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  • SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs
    bioRxiv. Immunol. Pub Date : 2020-10-26
    Shira Weingarten-Gabbay; Susan Klaeger; Siranush Sarkizova; Leah R Pearlman; Da-Yuan Chen; Matthew R Bauer; Hannah B Taylor; Hasahn L Conway; Christopher H Tomkins-Tinch; Yaara Finkel; Aharon Nachshon; Matteo Gentili; Keith D Rivera; Derin B Keskin; Charles M Rice; Karl R Clauser; Nir Hacohen; Steven A Carr; Jennifer G Abelin; Mohsan Saeed; Pardis C Sabeti

    T cell-mediated immunity may play a critical role in controlling and establishing protective immunity against SARS-CoV-2 infection; yet the repertoire of viral epitopes responsible for T cell response activation remains mostly unknown. Identification of viral peptides presented on class I human leukocyte antigen (HLA-I) can reveal epitopes for recognition by cytotoxic T cells and potential incorporation

    更新日期:2020-10-27
  • Differences in pulmonary innate lymphoid cells are dependent on mouse age, sex and strain
    bioRxiv. Immunol. Pub Date : 2020-10-26
    Svenja Loering; Guy John-Malcolm Cameron; Nirmal P Bhatt; Gabrielle T Belz; Paul S Foster; Phil M Hansbro; Malcolm R Starkey

    Innate lymphoid cells (ILC) are resident in the lung and are involved in both the maintenance of homeostasis and the pathogenesis of respiratory diseases. In this study, murine lung ILC were characterised using flow cytometry and the impact of mouse age, sex and strain were assessed. Lung ILC were found as early as postnatal day 4 and numbers peaked at 2 weeks, and then decreased as the lung matured

    更新日期:2020-10-27
  • Single-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte signatures of bacterial control
    bioRxiv. Immunol. Pub Date : 2020-10-26
    Hannah Priyadarshini Gideon; Travis K Hughes; Marc H Wadsworth; Ang A. Tu; Todd M Gierahn; Forrest H Hopkins; Jun-Rong Wei; Conner Kummerlowe; Nicole L Grant; Kievershen Nargan; JiaYao Phuah; H. Jacob Borish; Pauline Maiello; Alexander G White; Sharie Keanne C Ganchua; Amy Myers; Cassaundra Ameel; Catherine T. Cochran; Sarah K Nyquist; Joshua Mark Peters; Jaime A Tomko; Lonnie James Frye; Jacob Rosenberg;

    In humans and nonhuman primates, Mycobacterium tuberculosis lung infection yields a complex multicellular structure: the tuberculosis granuloma. All granulomas are not equivalent, however, even within the same host: in some, local immune activity promotes bacterial clearance, while in others, it allows persistence or outgrowth. Here, we used single-cell RNA-sequencing to define holistically cellular

    更新日期:2020-10-27
  • TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
    bioRxiv. Immunol. Pub Date : 2020-10-26
    Nayan D Bhattacharyya; Claudio Counoupas; Lina Daniel; Guoliang Zhang; Staurt J Cook; Taylor A Cootes; Sebastian A Stifter; David G Bowen; Patrick Bertolino; Warwick J Britton; Carl G Feng

    The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4+ T cells with different pMHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition nor

    更新日期:2020-10-27
  • The allosteric modulation of Complement C5 by knob domain peptides
    bioRxiv. Immunol. Pub Date : 2020-10-25
    Alex Macpherson; Maisem Laabei; Zainab Ahdash; Melissa A Graewert; James Birtley; Sarah Schulze; Susan Crennell; Sarah Robinson; Ben Holmes; Vladas Oleinikovas; Per H Nilsson; James Snowden; Victoria Ellis; Tom Eirik Mollnes; Charlotte M Deane; Dmitri I Svergun; Alastair Lawson; Jean van den Elsen

    To overcome limited germline combinatorial diversity, bovines have evolved a subset of antibodies with ultra-long CDRH3 regions that harbour cysteine-rich knob domains. To produce affinity-maturated peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug

    更新日期:2020-10-27
  • Dysregulation of Pulmonary Responses in Severe COVID-19
    bioRxiv. Immunol. Pub Date : 2020-10-25
    Dandan Wu; Xuexian Yang

    Patients with coronavirus disease 2019 (COVID-19) predominantly have a respiratory tract infection with various symptoms and high mortality is associated with respiratory failure second to severe disease. The risk factors leading to severe disease remain unclear. Here, we reanalyzed a published single-cell RNA-Seq (scRNA-Seq) dataset and found that bronchoalveolar lavage fluid (BALF) of patients with

    更新日期:2020-10-27
  • Bifidobacteria-mediated immune system imprinting early in life
    bioRxiv. Immunol. Pub Date : 2020-10-25
    Bethany Henrick; Lucie Rodriguez; Lakshmi Kanth Tadepally; Christian Pou; Ewa Henckel; Axel Olin; Jun Wang; Jaromir Mikes; Ziyang Tan; Yang Chen; Amy M Ehrlich; Anna Karin Bernhardsson; Constantin Habimana Mugabo; Ylva Ambrosiani; Anna Gustafsson; Stephanie Chew; Heather K Brown; Johann Prambs; Kajsa Bohlin; Ryan D Mitchell; Mark A Underwood; Jennifer T Smilowitz; Bruce J German; Steven A Frese; Petter

    Immune-microbe interactions early in life influence an individual's risk of developing allergies, asthma and some autoimmune disorders. Breastfeeding helps guide the development of healthy immune-microbe relationships, in part by providing nutrients to specialized microbes that in turn benefit the host and its developing immune system. Such bacteria having co-evolved with humans are associated with

    更新日期:2020-10-27
  • Immunoglobulins, MHC and T Cell receptors genes in Cetaceans
    bioRxiv. Immunol. Pub Date : 2020-10-25
    Francisco Gambon Deza

    Cetaceans correspond to mammals that have returned to the marine environment. Adaptive changes are very significant with the conversion of the limbs into flippers. It is studied the changes that have occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant regions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgD gene, which is composed

    更新日期:2020-10-27
  • Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Jim Boonyaratanakornkit; Suruchi Singh; Connor Weidle; Justas Rodarte; Ramasamy Bakthavatsalam; Jonathan Perkins; Guillaume B.E. Stewart-Jones; Peter D. Kwong; Andrew T. McGuire; Marie Pancera; Justin J Taylor

    Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. Unfortunately, an effective vaccine or therapeutic is not currently available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell

    更新日期:2020-10-27
  • Single cell transcriptional profiling reveals helper, effector, and regulatory MAIT cell populations enriched during homeostasis and activation
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Charles Kyriakos Vorkas; Chirag Krishna; Kelin Li; Jeff Aube; Linas Mazutis; Christina S Leslie; Michael Glickman

    Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant T cell receptor, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of

    更新日期:2020-10-27
  • Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Sergio Triana; Camila Metz Zumaran; Carlos Ramirez; Carmon Kee; Patricio Doldan; Mohammed Shahraz; Daniel Schraivogel; Andreas R. Gschwind; Lars M. Steinmetz; Carl Herrmann; Theodore Alexandrov; Steeve Boulant; Megan Lynn Stanifer

    Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target

    更新日期:2020-10-27
  • A derivative of the D5 monoclonal antibody that targets the gp41 N-heptad repeat of HIV-1 with broad tier-2 neutralizing activity
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Adonis A. Rubio; Maria V. Filsinger Interrante; Benjamin N. Bell; Clayton L. Brown; Celia C. LaBranche; David C. Montefiori; Peter S. Kim

    HIV-1 infection is initiated by the viral glycoprotein Env, which, after interaction with cellular coreceptors, adopts a transient conformation known as the pre-hairpin intermediate (PHI). The N-heptad repeat (NHR) is a highly conserved region of gp41 exposed in the PHI; it is the target of the FDA-approved drug enfuvirtide and of neutralizing monoclonal antibodies (mAbs). However, to date these mAbs

    更新日期:2020-10-27
  • Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Tejram Sahu; Ella J. Gehrke; Yevel Flores-Garcia; Godfree Mlambo; Julia D. Romano; Isabelle Coppens

    Genetically-attenuated sporozoite vaccines can elicit long-lasting protection against malaria but pose risks of breakthrough infection. Chemoprophylaxis vaccination (CVac) has proven to be the most effective vaccine strategy against malaria. Though CVac with WT sporozoites confers better immunity, the overhanging threat of drug resistance limits its use as a vaccine. Here, we demonstrate that a liver

    更新日期:2020-10-27
  • Targeting CSF-1 ameliorates experimental autoimmune encephalomyelitis by depleting inflammatory monocytes and microglia in the central nervous system without affecting quiescent microglia
    bioRxiv. Immunol. Pub Date : 2020-10-24
    Daniel Hwang; Larissa Lumi Watanabe Ishikawa; Alexandra Boehm; Ziver Sahin; Giacomo Casella; Soohwa Jang; Maryamsadat Seyedsadr; Michael V. Gonzalez; James P. Garifallou; Hakon Hakonarson; Guang-Xian Zhang; Abdolmohamad Rostami; Bogoljub Ciric

    Multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by extensive infiltration of myeloid cells into the central nervous system (CNS). Although myeloid cells are essential to MS/EAE pathology, none of the current MS therapies specifically target them. A promising strategy for bridging this gap may be targeting the biological activity

    更新日期:2020-10-27
  • Oral immunization of broilers with chitosan nano-encapsulated extracellular and cell wall proteins of necrotic enteritis-induced Clostridium perfringens
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Nour Muinis Ramadan; Gabriel O Akerele; Sankar Renu; Gourapura Renukaradhya; Ramesh Selvaraj

    Currently, there is no commercial vaccine to control Clostridium perfringens (CP) or necrotic enteritis – a clinically and economically devastating disease. Two chitosan-nanoparticle encapsulated CP (CNP-CP) vaccines using extracellular proteins (ECP) and cell wall proteins (CWP) were synthesized: a CNP-CP ECP + CWP vaccine (SC vaccine) and a CNP-CP ECP + CWP surface-adsorbed CWP vaccine (SCC vaccine)

    更新日期:2020-10-27
  • The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Thomas Demoulins; Melanie Bruegger; Beatrice Zumhehr; Blandina Oliveira Esteves; Kemal Mehinagic; Amal Fahmi; Loic Borcard; Adriano Taddeo; Horst Posthaus; Charaf Benarafa; Nicolas Ruggli; Marco P Alves

    The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the specific features of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a state-of-the-art model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early

    更新日期:2020-10-27
  • Single cell RNA-seq reveals immunosuppressive gastric stem-like cancer cells as a poor prognostic factor
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Hong Kai Lee; Kok Siong Ang; Marion Chevrier; Michelle Goh; Jingjing Ling; Vivien Koh; Xiaomeng Zhang; Jia Chi Tan; Nicole Lee; Sergio Erdal Irac; Ze Ming Lim; Josephine Lum; Alicia Tay; Charles Antoine Dutertre; Carolyn Tang; Calista Wong; Mai Chan Lau; Chun Jye Lim; Samuel Wen Jin Chuah; Sherlly Lim; Joe Poh Sheng Yeong; Valerie Chew; Anis Larbi; Amit Singhal; Michael Poidinger; Matthew Chau Hsien

    The tumor microenvironment is characterized by high cellular heterogeneity and a complex network of cell-cell communications. Analysis at the single cell level is required to dissect this complexity. Here we apply single-cell full-length transcriptome sequencing to analyze 3443 cells from paired normal-adjacent and tumor tissues of 15 gastric cancer patients with different histological profiles. Among

    更新日期:2020-10-27
  • Integration, exploration, and analysis of high-dimensional single-cell cytometry data using Spectre
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Thomas Myles Ashhurst; Felix Marsh-Wakefield; Givanna Haryono Putri; Alanna Gabrielle Spiteri; Diana Shinko; Mark Norman Read; Adrian Lloyd Smith; Nicholas Jonathan Cole King

    As the size and complexity of high-dimensional cytometry data continue to expand, comprehensive, scalable, and methodical computational analysis approaches are essential. Yet, contemporary clustering and dimensionality reduction tools alone are insufficient to analyze or reproduce analyses across large numbers of samples, batches, or experiments. Moreover, approaches that allow for the integration

    更新日期:2020-10-27
  • Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really "Sinful"?
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Tal Einav; Martina Kosikova; Peter Radvak; Yuan-Chia Kuo; Hyung Joon Kwon; Hang Xie

    The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated vaccination. In

    更新日期:2020-10-27
  • mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Susanne Rauch; Nicole Roth; Kim Schwendt; Mariola Fotin-Mleczek; Stefan O. Mueller; Benjamin Petsch

    The devastating SARS-CoV-2 pandemic demands rapid vaccine development and large scale production to meet worldwide needs. mRNA vaccines have emerged as one of the most promising technologies to address this unprecedented challenge. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle (LNP) encapsulated non-modified mRNA vaccine that encodes the full length, pre-fusion

    更新日期:2020-10-27
  • Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Amanda F. Alexander; Hannah Forbes; Kathryn Miller-Jensen

    Following TLR4 stimulation of macrophages, negative feedback mediated by the anti-inflammatory cytokine IL-10 limits the inflammatory response. However, extensive cell-to-cell variability in TLR4-stimulated cytokine secretion raises questions about how negative feedback is robustly implemented. To explore this, we characterized the TLR4-stimulated secretion program in primary murine macrophages using

    更新日期:2020-10-27
  • Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Emelyne Lécuyer; Tiphaine Le Roy; Aurélie Gestin; Amélie Lacombe; Catherine Philippe; Maharajah Ponnaiah; Jean-Baptiste Huré; Magali Fradet; Farid Ichou; Samira Boudebbouze; Thierry Huby; Emmanuel Gautier; Moez Rhimi; Emmanuelle Maguin; Nathalie Kapel; Philippe Gérard; Nicolas Venteclef; Michèle Garlatti; Benoit Chassaing; Philippe Lesnik

    Excess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this

    更新日期:2020-10-27
  • Adenosine diphosphate contributes to wound healing in diabetic mice through P2Y1 and P2Y12 receptors activation
    bioRxiv. Immunol. Pub Date : 2020-10-23
    Paula A. Borges; Ingrid Waclawiak; Janaína L. Georgii; Janaína F. Barros; Vanderlei S. Fraga-Junior; Felipe S. Lemos; Thaís Russo-Abrahão; Elvira M. Saraiva; Christina M. Takiya; Robson Coutinho-Silva; Carmen Penido; Claudia Mermelstein; José R. Meyer-Fernandes; Fábio B. Canto; Josiane S. Neves; Paulo A. Melo; Claudio Canetti; Claudia F. Benjamim

    Several studies have shown the importance of purinergic signaling in various inflammatory dis-eases. In diabetes mellitus, there is an increase in the activity of some nucleotidases suggesting that this signaling may be affected in the diabetic skin. Thus, the aim of our study was to inves-tigate the effect of ADP on wound healing in diabetic skin. Swis and C57BL/6 mice were pharmacologic induced to

    更新日期:2020-10-27
  • The PRC2-dependent epigenetic reprograming of the bladder epithelium exacerbates urinary tract infections
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Chunming Guo; Mingyi Zhao; Xinbing Sui; Zarine Balsara; Songhui Zhai; Ping Zhu; Xue Li

    Mucosal imprint sensitizes recurrent urinary tract infections (UTIs), a significant health and quality of life burden worldwide, which are associated with heightened inflammatory host response, severe basal cell hyperplasia and impaired superficial cell differentiation. Here, we show that bladder infections induce expression of Ezh2, the methyltransferase of polycomb repressor complex 2 (PRC2)-dependent

    更新日期:2020-10-27
  • Lymphatic PD-L1 expression restricts tumor-specific CD8+ T cell responses
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Stefan Cap; Manuel Dihr; Nikola Cousin; Carlotta Tacconi; Michael Detmar; Lothar C. Dieterich

    Lymph node (LN)-resident lymphatic endothelial cells (LECs) mediate peripheral tolerance by presentation of self-antigens on MHC-I and constitutive expression of T cell inhibitory molecules, including PD-L1. PD-L1 is also induced in tumor-associated LECs but the specific role of lymphatic PD-L1 in tumor immunity has remained unknown. We generated a mouse model lacking lymphatic PD-L1 expression and

    更新日期:2020-10-27
  • Parabacteroides distasonis enhances Type 1 Diabetes autoimmunity via molecular mimicry
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Qian Huang; I-Ting Chow; Claudia Brady; Amol Raisingani; Danmeng Li; David A. Ostrov; Mark A. Atkinson; William W. Kwok; C. Ronald Kahn; Emrah Altindis

    Type 1 Diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β-cells. Focusing on the main insulin epitope, insulin B-chain 9-23 (insB:9-23), we explored whether a microbial insB:9-23 mimic could modulate T1D. We now demonstrate that a microbial insB:9-23 mimic of Parabacteroides distasonis, a human gut commensal, exclusively stimulates non-obese diabetic (NOD) mouse T

    更新日期:2020-10-27
  • Epstein-Barr virus promotes survival through germinal center light zone chromatin architecture
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Joanne Dai; Emma Heckenberg; Lingyun Song; Gregory E. Crawford; Micah A. Luftig

    BFL-1 is an understudied anti-apoptotic protein upregulated in cancer and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs). We have previously shown that BFL23 1 is regulated through viral EBNA3A-mediated alterations in B-cell chromatin conformation (Price et al., 2017). Here, we extend those findings to define cis- and trans-acting factors that regulate BFL-1 in LCLs and reliance

    更新日期:2020-10-27
  • Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Stefania Capone; Angelo Raggioli; Michela Gentile; Simone Battella; Armin Lahm; Andrea Sommella; Alessandra Maria Contino; Richard A. Urbanowicz; Romina Scala; Federica Barra; Adriano Leuzzi; Eleonora Lilli; Giuseppina Miselli; Alessia Noto; Maria Ferraiuolo; Francesco Talotta; Theocharis Tsoleridis; Concetta Castilletti; Giulia Matusali; Francesca Colavita; Daniele Lapa; Silvia Meschi; Maria Capobianchi;

    The COVID-19 pandemic caused by the emergent SARS-CoV-2 coronavirus threatens global public health and there is an urgent need to develop safe and effective vaccines. Here we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV2. We show that our vaccine candidate, GRAd-COV2

    更新日期:2020-10-27
  • Mechanism of negative regulation of NF-κB by N4BP1
    bioRxiv. Immunol. Pub Date : 2020-10-22
    Hexin Shi; Lei Sun; Ying Wang; Aijie Liu; Xiaoming Zhan; Xiaohong Li; Miao Tang; Priscilla Anderton; Sara Hildebrand; Jiexia Quan; Sara Ludwig; Eva Marie Y. Moresco; Bruce Beutler

    Many immune responses depend upon activation of NF-κB, a key transcription factor in the elicitation of a cytokine response. Here we demonstrate that N4BP1 inhibited TLR-dependent activation of NF-κB by interacting with the NF-κB signaling essential modulator (NEMO, also known as IκB kinase γ) to attenuate NEMO-NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like

    更新日期:2020-10-27
  • Multi-omic Single-cell Atlas Reveals Broad Ex Vivo Effects on Human Immunobiology
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Adam K. Savage; Miriam V. Gutschow; Tony Chiang; Kathy Henderson; Richard Green; Monica Chaudhari; Elliott Swanson; Alexander T. Heubeck; Nina Kondza; Kelli C. Burley; Palak C. Genge; Cara Lord; Tanja Smith; Aldan Beaubien; Jeff Goldy; Hamid Bolouri; Jane H. Buckner; Paul Meijer; Ernest M. Coffey; Xiao-jun Li; Peter J. Skene; Troy R. Torgerson; Thomas F. Bumol

    Multi-omic profiling of human peripheral blood is increasingly utilized to identify biomarkers and pathophysiologic mechanisms of disease. The importance of these platforms in clinical and translational studies led us to investigate the impact of delayed blood processing on the numbers and state of peripheral blood mononuclear cells (PBMC) and on the plasma proteome. Similar to previous studies, we

    更新日期:2020-10-27
  • Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Bhagwati Khatri; James Keeble; Belinda Dagg; Daryan A. Kaveh; Philip J. Hogarth; Mei Mei Ho

    In this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette Guerin (BCG) Danish doses from 300,000 to 30 CFU/mouse, followed by either immunogenicity evaluation or aerosol infection with Mycobacterium tuberculosis (a laboratory strain H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant

    更新日期:2020-10-27
  • Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Rajan Guha; Anna Mathioudaki; Safiatou Doumbo; Didier Doumtabe; Jeff Skinner; Gunjan Arora; Shafiuddin Siddiqui; Shanping Li; Kassoum Kayentao; Aissata Ongoiba; Judith Zaugg; Boubacar Traore; Peter D. Crompton

    In malaria-naive children and adults, Plasmodium falciparum-infected red blood cells (Pf-iRBCs) trigger fever and other symptoms of systemic inflammation. However, in endemic areas where individuals experience repeated Pf infections over many years, the risk of Pf-iRBC-triggered inflammatory symptoms decreases with cumulative Pf exposure. The molecular mechanisms underlying these clinical observations

    更新日期:2020-10-27
  • Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and their Augmentation by Compact Peptide Sets
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Ge Liu; Brandon Carter; David K. Gifford

    Subunit vaccines induce immunity to a pathogen by presenting a component of the pathogen and thus inherently limit the representation of pathogen peptides for cellular immunity based memory. We find that SARS-CoV-2 subunit peptides may not be robustly displayed by the Major Histocompatibility Complex (MHC) molecules in certain individuals. We introduce an augmentation strategy for subunit vaccines

    更新日期:2020-10-27
  • Mitohormesis reprograms macrophage metabolism to enforce tolerance
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Greg A. Timblin; Kevin M. Tharp; Breanna Ford; Janet M. Winchenster; Jerome Wang; Stella Zhu; Rida I. Khan; Shannon K. Louie; Anthony T. Iavarone; Johanna ten Hoeve; Daniel K. Nomura; Andreas Stahl; Kaoru Saijo

    Macrophages generate mitochondrial reactive oxygen and electrophilic species (mtROS, mtRES) as antimicrobials during Toll-like receptor (TLR)-dependent inflammatory responses. Whether mitochondrial stress caused by these molecules impacts macrophage function is unknown. Here we demonstrate that both pharmacologically- and lipopolysaccharide (LPS)-driven mitochondrial stress in macrophages triggers

    更新日期:2020-10-27
  • The magnitude of airway remodelling is not altered by distinct allergic inflammatory responses in BALB/c vs C57BL/6 mice, but matrix composition differs
    bioRxiv. Immunol. Pub Date : 2020-10-21
    James E Parkinson; Stella Pearson; Dominik Rückerl; Judith E Allen; Tara E Sutherland

    Airway inflammation in response to allergens is heterogenous with variability in immune phenotypes observed across asthmatic patients. Whilst inflammation, specifically type 2 immune responses, are thought to directly contribute to airway remodelling and pathology in asthma, clinical data suggests that neutralising type 2 cytokines do not necessarily alter disease pathogenesis. Here we show, using

    更新日期:2020-10-27
  • Preclinical study of DNA vaccines targeting SARS-CoV-2
    bioRxiv. Immunol. Pub Date : 2020-10-21
    Hiroki Hayashi; Jiao Sun; Yuka Yanagida; Takako Otera; Ritsuko Kubota-Kotetsu; Tatsuo Shioda; Chikako Ono; Yoshiharu Matsuura; Hisashi Arase; Shota Yoshida; Ryo Nakamaru; Ryoko Ide; Akiko Tenma; Sotaro Kawabata; Takako Ehara; Makoto Sakaguchi; Hideki Tomioka; Munehisa Shimamura; Sachiko Okamoto; Yasunori Amaishi; Hideto Chono; Junichi Mineno; Takano Komatsuno; Yoshimi Saito; Hiromi Rakugi; Ryuichi

    To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA or RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein)

    更新日期:2020-10-27
  • Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction
    bioRxiv. Immunol. Pub Date : 2020-10-20
    Bianca H Ventura Fernandes; Natália Martins Feitosa; Ana Paula Barbosa; Camila Gasque Bomfim; Anali M. B. Garnique; Francisco I. F. Gomes; Rafael T. Nakajima; Marco A. A. Belo; Silas Fernandes Eto; Dayanne Carla Fernandes; Guilherme Malafaia; Wilson G. Manrique; Gabriel Conde; Roberta R. C. Rosales; Iris Todeschini; Ilo Rivero; Edgar Llontop; German G. Sgro; Gabriel Umaji Oka; Natalia F Bueno; Fausto

    Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal

    更新日期:2020-10-27
  • Cyclic-di-GMP induces STING-dependent ILC2 to ILC1 shift during innate type 2 lung inflammation
    bioRxiv. Immunol. Pub Date : 2020-10-19
    Kellen J Cavagnero; Taylor A Doherty; Jana H Badrani; Luay H Naji; Lee Diego Lacasa; Allyssa N Strohm; Michael B Amadeo; Anthea S Leng

    Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is

    更新日期:2020-10-20
  • The central THαβ immunity associated cytokine: IL-10 has a strong anti-tumor ability toward established cancer models in vivo and toward cancer cells in vitro
    bioRxiv. Immunol. Pub Date : 2020-10-19
    Wanchung Hu

    Cancer immunotherapy is a promising new approach for cancer treatment. We propose to use a new host immunological pathway: THalpha/beta immunity for cancer treatment. THalpha/beta immunity is a natural host immunity which can be used IFN-alpha/beta and its major effectors are IL-10 and IL-15. Thus, we here used these cytokines for treatment both in a mice breast cancer 4T1 model and in a neuroblastoma

    更新日期:2020-10-20
  • The microbiota plays a critical role in the reactivity of lung immune components to innate ligands
    bioRxiv. Immunol. Pub Date : 2020-10-19
    Quentin Marquant; Daphne Laubreton; Carole Drajac; Elliot Mathieu; Edwige Bouguyon; Marie-Louise Noordine; Aude Remot; Sabine Riffault; Muriel Thomas; Delphyne Descamps

    The microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota can modulate reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific pathogen-free (SPF) and germ-free (GF) mice. Using

    更新日期:2020-10-20
  • SARS-CoV-2 genome-wide mapping of CD8 T cell recognition reveals strong immunodominance and substantial CD8 T cell activation in COVID-19 patients
    bioRxiv. Immunol. Pub Date : 2020-10-19
    Sunil Kumar Saini; Ditte Stampe Hersby; Tripti Tamhane; Helle Rus Povlsen; Susana Patricia Amaya Hernandez; Morten Nielsen; Anne Ortved Gang; Sine Reker Hadrup

    To understand the CD8+ T cell immunity related to viral protection and disease severity in COVID-19, we evaluated the complete SARS-CoV-2 genome (3141 MHC-I binding peptides) to identify immunogenic T cell epitopes, and determine the level of CD8+ T cell involvement using DNA-barcoded peptide-major histocompatibility complex (pMHC) multimers. COVID-19 patients showed strong T cell responses, with up

    更新日期:2020-10-20
  • Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes
    bioRxiv. Immunol. Pub Date : 2020-10-19
    Khun Zaw Latt; Jurgen Heymann; Joseph H Jessee; Avi Z Rosenberg; Celine C Berthier; Sean Eddy; Teruhiko Yoshida; Yongmei Zhao; Vicky Chen; George W Nelson; Margaret Cam; Parimal Kumar; Monika Mehta; Michael C Kelly; Matthias Kretzler; The Nephrotic Syndrome Study Network (NEPTUNE); The Accelerating Medicines Partnership in RA and SLE (AMP RA/SLE) consortium; Cheryl A Winkler; Jeffrey B Kopp

    The diagnosis of focal segmental glomerulosclerosis (FSGS) requires a renal biopsy, which is invasive and can be problematic in children and in some adults. We used single cell RNA-sequencing to explore disease-related cellular signatures in 23 urine samples from 12 FSGS subjects. We identified immune cells, predominantly monocytes, and renal epithelial cells, including podocytes. Analysis revealed

    更新日期:2020-10-20
  • Transovarial transmission fuels persistent infections of a core virome in the Chagas disease vector Rhodnius prolixus
    bioRxiv. Immunol. Pub Date : 2020-10-18
    Tarcisio Fontenele de Brito; Vitor Lima Coelho; Maira Arruda Cardoso; Ingrid Alexandre de Abreu Brito; Fides Lea Zenk; Nicola Iovino; Attilio Pane

    Triatomine assassin bugs comprise hematophagous insect vectors of Trypanosoma cruzi, the causative agent of the Chagas disease. Although the microbiome of these species has been investigated to some extent, only one virus infecting Triatoma infestans has been identified to date. Here, we describe for the first time seven (+) single-strand RNA viruses (RpV1-7) infecting Rhodnius prolixus, a primary

    更新日期:2020-10-19
  • CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells.
    bioRxiv. Immunol. Pub Date : 2020-10-17
    Charlotte A James; Yuexin Xu; Melissa S Aguilar; Lichen Jing; Erik D Layton; Martine Gilleron; Adriaan J Minnaard; Thomas Scriba; Cheryl L Day; Edus H Warren; David M Koelle; Chetan Seshadri

    CD4 and CD8 co-receptors define distinct lineages of T cells restricted by major histocompatibility complex (MHC) Class II and I molecules, respectively. Co-receptors interact with the T cell receptor (TCR) at the surface of MHC-restricted T cells to facilitate antigen recognition, thymic selection, and functional differentiation. T cells also recognize lipid antigens presented by CD1 molecules, but

    更新日期:2020-10-19
  • The JAK2-STAT pathway epigenetically regulates tolerized genes during the first encounter with bacterial antigens
    bioRxiv. Immunol. Pub Date : 2020-10-17
    Clara Lorente-Sorolla; Octavio Morante-Palacios; Antonio Garcia-Gomez; Laura Ciudad; Francesc Catala-Moll; Adolfo Ruiz-Sanmartin; Monica Martinez-Gallo; Ricard Ferrer-Roca; Juan Carlos Ruiz-Rodriguez; Damiana Alvarez-Errico; Esteban Ballestar

    Microbial challenges, such as widespread bacterial infection, induce endotoxin tolerance. This state of hyporesponsiveness to subsequent infections is mainly displayed by monocytes and macrophages. Endotoxin tolerance is generally acquired following a septic episode. In this study, we investigated DNA methylation changes during the acquisition of in vitro tolerance. We identified a set of TET2-mediated

    更新日期:2020-10-17
  • Naturally secreted bacterial outer membrane vesicles: potential platform for a vaccine against Campylobacter jejuni
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Ankita Singh; Afruja Khan; Tamal Ghosh; Samiran Mondal; Amirul Islam Mallick

    Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni ( C. jejuni ) infection remain significant public health risks in developing countries with substantial mortality and morbidity in humans, particularly in children under the age of five. Despite improved global awareness in sanitation and hygiene practices, including food safety measures, C. jejuni infections continue to rise

    更新日期:2020-10-17
  • Highly efficient CRISPR-Cas9-mediated gene knockout in primary human B cells for functional genetic studies of Epstein-Barr virus infection
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Ezgi Akidil; Manuel Albanese; Alexander Buschle; Adrian Ruhle; Oliver T Keppler; Wolfgang Hammerschmidt

    Gene editing is now routine in all prokaryotic and metazoan cells but has not received much attention in immune cells when the CRISPR-Cas9 technology was introduced in the field of mammalian cell biology less than ten years ago. This versatile technology has been successfully adapted for gene modifications in human myeloid cells and T cells, among others, but applications to human primary B cells have

    更新日期:2020-10-17
  • The Theory and Practice of the viral dose in neutralization assay: insights on SARS-CoV-2 "doublethink" effect.
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Eleonora Molesti; Alessandro Manenti; Marta Maggetti; Giulia Lapini; Alessandro Torelli; Emanuele Montomoli

    Due to the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for reliable high-throughput serological assays in order to evaluate the immunological responses against SARS-COV-2 virus and to enable population screening, as well as vaccines and drugs efficacy testing. Several serological assays for SARS-CoV-2 are now becoming available in the market

    更新日期:2020-10-17
  • Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Eszter Somogyi; Zsolt Csiszovszki; Levente Molnár; Orsolya Lőrincz; József Tóth; Sofie Pattijn; Jana Schockaert; Aurélie Mazy; István Miklós; Katalin Pántya; Péter Páles; Enikő R. Tőke

    We developed a global peptide vaccine against SARS-CoV-2 that addresses the dual challenges of heterogeneity in the immune responses of different individuals and potential heterogeneity of the infecting virus. PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides derived from all four major structural proteins of the SARS-CoV-2. Vaccine peptides were selected based on their frequency

    更新日期:2020-10-17
  • Abnormal Antibodies to Self-Carbohydrates in SARS-CoV-2 Infected Patients
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Dorothy L. Butler; Jeffrey C. Gildersleeve

    SARS-CoV-2 is a deadly virus that is causing the global pandemic coronavirus disease 2019 (COVID-19). Our immune system plays a critical role in preventing, clearing, and treating the virus, but aberrant immune responses can contribute to deleterious symptoms and mortality. Many aspects of immune responses to SARS-CoV-2 are being investigated, but little is known about immune responses to carbohydrates

    更新日期:2020-10-17
  • Antibody Response to a Nucleocapsid Epitope as a Marker for COVID-19 Disease Severity
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Sanjana Sen; Emily C Sanders; Kristin N Gabriel; Brian M Miller; Hariny M Isoda; Gabriela S Salcedo; Jason E Garrido; Rebekah P Dyer; Rie Nakajima; Aarti Jain; Alicia M Santos; Keertna Bhuvan; Delia F Tifrea; Joni L Ricks-Oddie; Philip L Felgner; Robert A Edwards; Sudipta Majumdar; Gregory A Weiss

    Characterization of antibody response to SARS-CoV-2 is urgently needed to predict COVID-19 disease trajectories. Ineffective antibodies or antibody-dependent enhancement (ADE) could derail patient immune responses, for example. ELISA and coronavirus antigen microarray (COVAM) analysis epitope-mapped plasma from 86 COVID-19 patients. The experiments identified antibodies to a 21-residue epitope from

    更新日期:2020-10-17
  • Early induction of SARS-CoV-2 specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Anthony T Tan; Martin Linster; Cheewah Tan; Nina Le Bert; Wanni Chia; Kamini Kunasegaran; Yan Zhuang; Christine YL Tham; Adeline Chia; Gavin James Smith; Barnaby Edward Young; Shirin Kalimuddin; Jenny GH Low; David Lye; Lin-Fa Wang; Antonio Bertoletti

    Virus-specific humoral and cellular immunity act synergistically to protect the host from viral infection. We interrogated the dynamic changes of virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from disease onset to convalescence or death. We quantified SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells

    更新日期:2020-10-17
  • Additional analyses exploring the hypothesized transdifferentiation of plasmablasts to developing neutrophils in severe COVID-19
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Aaron J Wilk; Arjun Rustagi; Nancy Q Zhao; Beth A Martin; Angela J Rogers; Catherine A Blish

    We thank Alquicira-Hernandez et al. for their reanalysis of our single-cell transcriptomic dataset profiling peripheral immune responses to severe COVID-19. We agree that careful analysis of single-cell sequencing data is important for generating cogent hypotheses but find several aspects of their criticism of our analysis to be problematic. Here we respond briefly to misunderstandings and inaccuracies

    更新日期:2020-10-17
  • Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Arinjay Banerjee; Nader El-Sayes; Patrick Budylowski; Daniel Richard; Hassaan Maan; Jennifer Aguiar; Kaushal Baid; Michael R. D'Agostino; Jann Catherine Ang; Benjamin J.-M. Tremblay; Sam Afkhami; Mehran Karimzadeh; Aaron T. Irving; Lily Yip; Mario A Ostrowski; Jeremy A Hirota; Robert Kozak; Terence D Capellini; Matthew S. Miller; Bo Wang; Samira Mubareka; Allison J. McGeer; Andrew G McArthur; Andrew

    Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies

    更新日期:2020-10-17
  • Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Marissa D Fahlberg; Robert V Blair; Lara A Doyle-Meyers; Cecily C Midkiff; Giorgio Zenere; Kasi E Russell-Lodrigue; Christopher J Monjure; Erin H Haupt; Toni P Penney; Gabrielle Lehmicke; Brienna M Threeton; Nadia Golden; Presan K Datta; Chad J Roy; Rudolph P Bohm; Nicholas J Maness; Tracy Fischer; Jay Rappaport; Monica Vaccari

    We investigated the immune events following SARS-CoV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a robust and rapid migration of monocytes expressing CD16 from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial

    更新日期:2020-10-17
  • Soluble mannose receptor induces pro-inflammatory macrophage activation and metaflammation
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Maria Embgenbroich; Hendrik JP van der Zande; Leonie Hussaarts; Jonas Schulte-Schrepping; Leonard R Pelgrom; Noemi Garcia-Tardon; Laura Schlautmann; Isabel Stoetzel; Kristian Handler; Joost M Lambooij; Anna Zawistowska-Deniziak; Lisa Hoving; Karin de Ruiter; Marjolein Wijngaarden; Hanno Pijl; Ko Willems van Dijk; Bart Everts; Vanessa van Harmelen; Maria Yazdanbakhsh; Joachim L Schultze; Bruno Guigas;

    Pro-inflammatory activation of macrophages in metabolic tissues is critically important in induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct, functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to a Src/Akt/NF-κB-mediated cellular

    更新日期:2020-10-17
  • Cross-reactive anti-hemagglutinin (HA) IgG responses are shaped by previous long-interval monovalent H5 vaccination and highly correlated with HA antigenic distance
    bioRxiv. Immunol. Pub Date : 2020-10-16
    Jiong Wang; Dongmei Li; Sheldon Perry; Shannon P Hilchey; Alexander Wiltse; John J Treanor; Mark Y Sangerst; Martin S Zand

    Avian H5 influenza is an emerging influenza strain with the potential for human pandemic spread. One unresolved issue in pandemic vaccine preparedness is to what extent a vaccine recall response depends on the interval between the priming and boosting vaccinations. In this study, we analyzed the anti-H5 HA IgG responses to an H5 A/Indonesia/5/2005 boosting vaccination in three cohorts: (1) a short

    更新日期:2020-10-17
  • Chitosan nanoparticle vaccine loaded with crude extracellular proteins of C. perfringens and Salmonella flagella is partially protective against necrotic enteritis in broiler chickens.
    bioRxiv. Immunol. Pub Date : 2020-10-15
    Gabriel O Akerele; Nour Ramadan; Muhammad Mortada; Revathi Shanmugasundaram; Sankar Renu; Gourapura Renukaradhya; Ramesh K Selvaraj

    Necrotic enteritis (NE) causes significant economic losses and food shortages world-wide. There are currently no licensed commercial vaccines against NE in broilers. Chitosan nanoparticles were formulated with extracellular proteins of C. perfringens surface-tagged with Salmonella flagellar proteins. One-day-old male broiler chicks were completely randomized to 3 treatments: Non-vaccinated non-challenged

    更新日期:2020-10-17
  • Preventing neutrophil from oxygen exposure allows their basal state maintenance
    bioRxiv. Immunol. Pub Date : 2020-10-15
    Louise Injarabian; Quentin Giai Gianetto; Veronique Witko-Sarsat; Benoit S Marteyn

    Neutrophils are the most abundant circulating white blood cells and are central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1 to 4% O2) to which they are well adapted. Neutrophils are atypical cells since they are mainly glycolytic, and highly susceptible to oxygen-exposure, which induces their activation and death, through

    更新日期:2020-10-17