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  • Serum Free Light Chains in Common Variable Immunodeficiency Disorders: Role in Differential Diagnosis and Association With Clinical Phenotype
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-10
    Riccardo Scarpa; Federica Pulvirenti; Antonio Pecoraro; Alessandra Vultaggio; Carolina Marasco; Roberto Ria; Sara Altinier; Nicolò Compagno; Davide Firinu; Mario Plebani; Marco De Carli; Andrea Matucci; Fabrizio Vianello; Angelo Vacca; Giuseppe Spadaro; Isabella Quinti; Carlo Agostini; Cinzia Milito; Francesco Cinetto

    We report on an observational, multicenter study of 345 adult CVID patients, designed to assess the diagnostic value and the clinical association of serum free light chain (sFLC) pattern in Common Variable Immunodeficiency disorders (CVID). Sixty CVID patients were tested twice in order to assess intraindividual variability of sFLC. As control groups we included 138 patients affected by undefined primary

    更新日期:2020-03-31
  • Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-17
    Dong Ling Tong; Karen E. Kempsell; Tamas Szakmany; Graham Ball

    Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS)

    更新日期:2020-03-31
  • Role of ADAM10 as a CD30 Sheddase in Classical Hodgkin Lymphoma
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-19
    Hinrich P. Hansen; Adriana F. Paes Leme; Michael Hallek

    Cancer cells generally recruit and influence non-malignant immune cells to support the tumor growth. Classical Hodgkin lymphoma (cHL) is a good example because the affected lymphoid tissue contains only a few malignant Hodgkin and Reed-Sternberg (H-RS) cells, which are supported by a massive infiltrate of lymphocytes, fibroblasts, and innate immune cells. The transmembrane receptor CD30, which is selectively

    更新日期:2020-03-31
  • Transcriptomic Analysis of Monocyte-Derived Non-Phagocytic Macrophages Favors a Role in Limiting Tissue Repair and Fibrosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-20
    Sergei Butenko; Senthil K. Satyanarayanan; Simaan Assi; Sagie Schif-Zuck; Noa Sher; Amiram Ariel

    Monocyte-derived macrophages are readily differentiating cells that adapt their gene expression profile to environmental cues and functional needs. During the resolution of inflammation, monocytes initially differentiate to reparative phagocytic macrophages and later to pro-resolving non-phagocytic macrophages that produce high levels of IFNβ to boost resolutive events. Here, we performed in-depth

    更新日期:2020-03-31
  • JunB Controls Intestinal Effector Programs in Regulatory T Cells
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-26
    Joshua D. Wheaton; Maria Ciofani

    Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors controlling tissue-specific gene expression in Tregs remain unclear. Here, we find that the AP-1 transcription factor JunB regulates the intestinal

    更新日期:2020-03-31
  • Tissue-Specific Factors Differentially Regulate the Expression of Antigen-Processing Enzymes During Dendritic Cell Ontogeny
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-27
    Karim Mahiddine; Chervin Hassel; Claire Murat; Maeva Girard; Sylvie Guerder

    Dendritic cells (DCs) form a collection of antigen-presenting cells (APCs) that are distributed throughout the body. Conventional DCs (cDCs), which include the cDC1 and cDC2 subsets, and plasmacytoid DCs (pDCs) constitute the two major ontogenically distinct DC populations. The pDCs complete their differentiation in the bone marrow (BM), whereas the cDC subsets derive from pre-committed BM precursors

    更新日期:2020-03-31
  • A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-27
    Harald Hampel; Filippo Caraci; A. Claudio Cuello; Giuseppe Caruso; Robert Nisticò; Massimo Corbo; Filippo Baldacci; Nicola Toschi; Francesco Garaci; Patrizia A. Chiesa; Steven R. Verdooner; Leyla Akman-Anderson; Félix Hernández; Jesús Ávila; Enzo Emanuele; Pedro L. Valenzuela; Alejandro Lucía; Mark Watling; Bruno P. Imbimbo; Andrea Vergallo; Simone Lista

    Neuroinflammation commences decades before Alzheimer's disease (AD) clinical onset and represents one of the earliest pathomechanistic alterations throughout the AD continuum. Large-scale genome-wide association studies point out several genetic variants—TREM2, CD33, PILRA, CR1, MS4A, CLU, ABCA7, EPHA1, and HLA-DRB5-HLA-DRB1—potentially linked to neuroinflammation. Most of these genes are involved

    更新日期:2020-03-31
  • Bacillus anthracis Poly-γ-D-Glutamate Capsule Inhibits Opsonic Phagocytosis by Impeding Complement Activation
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-28
    Shikhar Sharma; Rakesh Bhatnagar; Deepak Gaur

    Bacillus anthracis poly-γ-D-glutamic acid (PGA) capsule is an essential virulent factor that helps the bacterial pathogen to escape host immunity. Like other encapsulated bacterial species, the B. anthracis capsule may also inhibit complement-mediated clearance and ensure bacterial survival in the host. Previous reports suggest that B. anthracis spore proteins inhibit complement activation. However

    更新日期:2020-03-31
  • The Emerging Jamboree of Transformative Therapies for Autoimmune Diseases
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-28
    José M. Carballido; Camille Regairaz; Celine Rauld; Layla Raad; Damien Picard; Michael Kammüller

    Standard treatments for autoimmune and autoinflammatory disorders rely mainly on immunosuppression. These are predominantly symptomatic remedies that do not affect the root cause of the disease and are associated with multiple side effects. Immunotherapies are being developed during the last decades as more specific and safer alternatives to small molecules with broad immunosuppressive activity, but

    更新日期:2020-03-31
  • LOXL2 Inhibition Paves the Way for Macrophage-Mediated Collagen Degradation in Liver Fibrosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-02
    Mordehay Klepfish; Tamar Gross; Milena Vugman; Nikolaos A. Afratis; Sapir Havusha-Laufer; Eli Brazowski; Inna Solomonov; Chen Varol; Irit Sagi

    Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) proteins and enzymes, especially fibrillary collagens, and represents a major cause of morbidity and mortality worldwide. Lysyl oxidases (LOXs) drive covalent crosslinking of collagen fibers, thereby promoting stabilization and accumulation of liver fibrosis while limiting its resolution. Here we show in a carbon

    更新日期:2020-03-31
  • Targeting Chemokine—Glycosaminoglycan Interactions to Inhibit Inflammation
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-02
    Helena Crijns; Vincent Vanheule; Paul Proost

    Leukocyte migration into tissues depends on the activity of chemokines that form concentration gradients to guide leukocytes to a specific site. Interaction of chemokines with their specific G protein-coupled receptors (GPCRs) on leukocytes induces leukocyte adhesion to the endothelial cells, followed by extravasation of the leukocytes and subsequent directed migration along the chemotactic gradient

    更新日期:2020-03-31
  • Dynamic Interplay of Host and Pathogens in an Avian Whole-Blood Model
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-04
    Sravya Sreekantapuram; Teresa Lehnert; Maria T. E. Prauße; Angela Berndt; Christian Berens; Marc Thilo Figge; Ilse D. Jacobsen

    Microbial survival in blood is an essential step toward the development of disseminated diseases and blood stream infections. For poultry, however, little is known about the interactions of host cells and pathogens in blood. We established an ex vivo chicken whole-blood infection assay as a tool to analyze interactions between host cells and three model pathogens, Escherichia coli, Staphylococcus aureus

    更新日期:2020-03-31
  • Immunological Role of the Maternal Uterine Microbiota in Postpartum Hemorrhage
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-05
    Maria F. Escobar; Maria A. Hincapie; Juan S. Barona

    Recent metagenomics and microbiology studies have identified microorganisms that are typical of the fetoplacental unit. Considering this emerging evidence, the placenta, uterus, and the amniotic cavity are not sterile and not immune privileged. However, there is evidence for a beneficial interaction between active maternal immune system and the presence of commensal pathogens, which lead to an immune-tolerant

    更新日期:2020-03-31
  • Regulatory T Cells Beyond Autoimmunity: From Pregnancy to Cancer and Cardiovascular Disease
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-05
    Elisa Martini; Silvia Giugliano; Maria Rescigno; Marinos Kallikourdis

    The evolution of the full range of functions of regulatory T cells (Treg) coincides with the evolution of mammalian pregnancy. Accordingly, Treg function has been shown to be crucial for maternal-fetal tolerance and implantation. As reproduction is a key point of selective pressure, mammalian pregnancy may represent an evolutionary driver for the development of Treg. Yet beyond the chronological boundaries

    更新日期:2020-03-31
  • CD3ε+ Cells in Pigs With Severe Combined Immunodeficiency Due to Defects in ARTEMIS
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-05
    Adeline N. Boettcher; A. Giselle Cino-Ozuna; Yash Solanki; Jayne E. Wiarda; Ellie Putz; Jeana L. Owens; Sara A. Crane; Amanda P. Ahrens; Crystal L. Loving; Joan. E. Cunnick; Raymond R. R. Rowland; Sara E. Charley; Jack C. M. Dekkers; Christopher K. Tuggle

    Severe combined immunodeficiency (SCID) is described as the lack of functional T and B cells. In some cases, mutant genes encoding proteins involved in the process of VDJ recombination retain partial activity and are classified as hypomorphs. Hypomorphic activity in the products from these genes can function in the development of T and B cells and is referred to as a leaky phenotype in patients and

    更新日期:2020-03-31
  • The Nexus Between Periodontal Inflammation and Dysbiosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Thomas E. Van Dyke; P. Mark Bartold; Eric C. Reynolds

    The nexus between periodontal inflammation and the polymicrobial biofilm in the gingival sulcus is critical to understanding the pathobiology of periodontitis. Both play a major role in the etiology and pathogenesis of periodontal diseases and each reinforces the other. However, this nexus is also at the center of a significant conundrum for periodontology. For all mucosal polymicrobial biofilms, the

    更新日期:2020-03-31
  • Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Kathrin Balz; Lilith Trassl; Valerie Härtel; Philipp P. Nelson; Chrysanthi Skevaki

    Heterologous immunity (H.I.) is a consequence of an encounter with a specific antigen, which can alter the subsequent immune response to a different antigen. This can happen at the innate immune system level—often called trained immunity or innate immune memory—and/or at the adaptive immune system level involving T memory cells and antibodies. Viruses may also induce T cell-mediated H.I., which can

    更新日期:2020-03-31
  • BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3+ Treg Polarization
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Jun-Ai Zhang; Yuan-Bin Lu; Wan-Dang Wang; Gan-Bin Liu; Chen Chen; Ling Shen; Hou-Long Luo; Huan Xu; Ying Peng; Hong Luo; Gui-Xian Huang; Du-Du Wu; Bi-Ying Zheng; Lai-Long Yi; Zheng W. Chen; Jun-Fa Xu

    Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid

    更新日期:2020-03-31
  • TREML4 Promotes Inflammatory Programs in Human and Murine Macrophages and Alters Atherosclerosis Lesion Composition in the Apolipoprotein E Deficient Mouse
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-19
    Marieli Gonzalez-Cotto; Liang Guo; Megan Karwan; Shurjo K. Sen; Jennifer Barb; Carlos J. Collado; Fathi Elloumi; Erika M. Palmieri; Kimberly Boelte; Frank D. Kolodgie; Aloke V. Finn; Leslie G. Biesecker; Daniel W. McVicar

    The Triggering Receptor Expressed on Myeloid cells-like 4 (TREML4) is a member of the TREM receptor family, known modulators of inflammatory responses. We have previously found that TREML4 expression positively correlates with human coronary arterial calcification (CAC). However, the role of TREML4 in the pathogenesis of cardiovascular disease remains incompletely defined. Since macrophages play a

    更新日期:2020-03-30
  • Fish c-Jun N-Terminal Kinase (JNK) Pathway Is Involved in Bacterial MDP-Induced Intestinal Inflammation
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-28
    Fufa Qu; Wenqian Xu; Zhangren Deng; Yifang Xie; Jianzhou Tang; Zhiguo Chen; Wenjie Luo; Ding Xiong; Dafang Zhao; Jiamei Fang; Zhigang Zhou; Zhen Liu

    The c-Jun NH2-terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases that play critical roles in the pathological process in species ranging from insects to mammals. However, the function of JNKs in bacteria-induced intestinal inflammation is still poorly understood. In this study, a fish JNK (CiJNK) pathway was identified, and its potential roles in bacterial

    更新日期:2020-03-30
  • Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-25
    Waqas Azeem; Ragnhild Maukon Bakke; Silke Appel; Anne Margrete Øyan; Karl-Henning Kalland

    The transcription factor β-catenin is able to induce tolerogenic/anti-inflammatory features in different types of dendritic cells (DCs). Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. We wanted to investigate the hypothesis that aberrant differentiation or induction of dual pro- and anti-inflammatory

    更新日期:2020-03-30
  • Expression of IL-33 Receptor Is Significantly Up-Regulated in B Cells During Pregnancy and in the Acute Phase of Preterm Birth in Mice
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-26
    Natalin Valeff; Lorena Juriol; Florencia Quadrana; Damián Oscar Muzzio; Marek Zygmunt; Maria Florencia Quiroga; María Silvia Ventimiglia; Federico Jensen

    Interleukin-33 (IL-33) is a mucosal alarmin belonging to the IL-1 cytokine family and is now recognized to have a key role in innate and adaptive immunity, contributing to tissue homeostasis and response to environmental stresses. In addition, IL-33 has also been shown to work as a positive regulator that initiates and maintains a Th2 immune response. In the context of pregnancy, it has been recently

    更新日期:2020-03-30
  • Syndecan 4 Upregulation on Activated Langerhans Cells Counteracts Langerin Restriction to Facilitate Hepatitis C Virus Transmission
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-05
    Bernadien M. Nijmeijer; Julia Eder; Catharina J. M. Langedijk; Tanja M. Kaptein; Sofie Meeussen; Pascale Zimmermann; Carla M. S. Ribeiro; Teunis B. H. Geijtenbeek

    Sexually transmitted Hepatitis C virus (HCV) infections and high reinfections are a major concern amongst men who have sex with men (MSM) living with HIV-1 and HIV-negative MSM. Immune activation and/or HIV-1 coinfection enhance HCV susceptibility via sexual contact, suggesting that changes in immune cells or external factors are involved in increased susceptibility. Activation of anal mucosal Langerhans

    更新日期:2020-03-30
  • Microglial Corpse Clearance: Lessons From Macrophages
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-05
    Mar Márquez-Ropero; Eva Benito; Ainhoa Plaza-Zabala; Amanda Sierra

    From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage

    更新日期:2020-03-30
  • Molecular and Functional Analysis of Pore-Forming Toxin Monalysin From Entomopathogenic Bacterium Pseudomonas entomophila
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Saori Nonaka; Emil Salim; Koki Kamiya; Aki Hori; Firzan Nainu; Rangga Meidianto Asri; Ayu Masyita; Takumi Nishiuchi; Shoji Takeuchi; Noriyuki Kodera; Takayuki Kuraishi

    Pseudomonas entomophila is a highly pathogenic bacterium that infects insects. It is also used as a suitable model pathogen to analyze Drosophila's innate immunity. P. entomophila's virulence is largely derived from Monalysin, a β-barrel pore-forming toxin that damages Drosophila tissues, inducing necrotic cell death. Here we report the first and efficient purification of endogenous Monalysin and its

    更新日期:2020-03-30
  • Hepatitis B Core Antigen Impairs the Polarization While Promoting the Production of Inflammatory Cytokines of M2 Macrophages via the TLR2 Pathway
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-09
    Hongyu Yi; Ye Zhang; Xiaofei Yang; Mengyuan Li; Haifeng Hu; Jie Xiong; Ning Wang; Jingyi Jin; Yusi Zhang; Yun Song; Xian Wang; Lihua Chen; Jianqi Lian

    Although several evidences suggesting the vital roles that innate immunity plays in the persistence and elimination of chronic hepatitis B virus (CHB) infection, the exact mechanism is still complicated. Here, we successfully polarized monocytes derived from healthy human peripheral blood mononuclear cells (PBMCs) into M1/M2 macrophages and detected the effects of hepatitis B core antigen (HBcAg) on

    更新日期:2020-03-30
  • Liver, Tumor and Viral Hepatitis: Key Players in the Complex Balance Between Tolerance and Immune Activation
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-10
    Matti Sällberg; Anna Pasetto

    Liver cancer is the third most common cause of cancer related death in the World. From an epidemiological point of view the risk factors associated to primary liver cancer are mainly viral hepatitis infection and alcohol consumption. Even though there is a clear correlation between liver inflammation, cirrhosis and cancer, other emerging liver diseases (like fatty liver) could also lead to liver cancer

    更新日期:2020-03-30
  • Removal of Mannose-Ending Glycan at Asn2118 Abrogates FVIII Presentation by Human Monocyte-Derived Dendritic Cells
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-19
    Sandrine Delignat; Julie Rayes; Suryasarathi Dasgupta; Bagirath Gangadharan; Cécile V. Denis; Olivier D. Christophe; Jagadeesh Bayry; Srinivas V. Kaveri; Sébastien Lacroix-Desmazes

    The development of an immune response against therapeutic factor VIII is the major complication in hemophilia A patients. Oligomannose carbohydrates at N239 and/or N2118 on factor VIII allow its binding to the macrophage mannose receptor expressed on human dendritic cells, thereby leading to factor VIII endocytosis and presentation to CD4+ T lymphocytes. Here, we investigated whether altering the interaction

    更新日期:2020-03-30
  • Complement-Independent Modulation of Influenza A Virus Infection by Factor H
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-13
    Valarmathy Murugaiah; Praveen M. Varghese; Soad M. Saleh; Anthony G. Tsolaki; Salman H. Alrokayan; Haseeb A. Khan; Kate S. Collison; Robert B. Sim; Béatrice Nal; Futwan A. Al-Mohanna; Uday Kishore

    The complement system is an ancient innate immune defense mechanism that can recognize molecular patterns on the invading pathogens. Factor H, as an inhibitor of the alternative pathway, down-regulates complement activation on the host cell surface. Locally synthesized factor H at the site of infection/injury, including lungs, can act as a pattern recognition molecule without involving complement activation

    更新日期:2020-03-30
  • δ-Opioid Receptors, microRNAs, and Neuroinflammation in Cerebral Ischemia/Hypoxia
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-24
    Yi-Meng Chen; Xiao-Zhou He; Shu-Ming Wang; Ying Xia

    Hypoxia and ischemia are the main underlying pathogenesis of stroke and other neurological disorders. Cerebral hypoxia and/or ischemia (e.g., stroke) can lead to neuronal injury/death and eventually cause serious neurological disorders or even death in the patients. Despite knowing these serious consequences, there are limited neuroprotective strategies against hypoxic and ischemic insults in clinical

    更新日期:2020-03-30
  • Molecular Fingerprints of Borderline Changes in Kidney Allografts Are Influenced by Donor Category
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-24
    Petra Hruba; Zdenek Krejcik; Michaela Dostalova Merkerova; Jiri Klema; Viktor Stranecky; Janka Slatinska; Jana Maluskova; Eva Honsova; Ondrej Viklicky

    The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent

    更新日期:2020-03-30
  • Induction of Cross-Reactive and Protective Antibody Responses After DNA Vaccination With MHCII-Targeted Stem Domain From Influenza Hemagglutinin
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-25
    Gunnveig Grødeland; Marta Baranowska-Hustad; Justin Abadejos; Tanya R. Blane; John Teijaro; David Nemazee; Bjarne Bogen

    Novel and more broadly protective vaccines against influenza are needed to efficiently meet antigenic drift and shift. Relevant to this end, the stem domain of hemagglutinin (HA) is highly conserved, and antibodies specific for epitopes located to the stem have been demonstrated to be able to confer broad protection against various influenza subtypes. However, a remaining challenge is to induce antibodies

    更新日期:2020-03-30
  • NKG2D Ligand Shedding in Response to Stress: Role of ADAM10
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-26
    Alessandra Zingoni; Elisabetta Vulpis; Luisa Loconte; Angela Santoni

    NKG2D is an activating receptor expressed by NK cells and some subsets of T cells and represents a major recognition receptor for detection and elimination of cancer cells. The ligands of NKG2D are stress-induced self-proteins that can be secreted as soluble molecules by protease-mediated cleavage. The release of NKG2D ligands in the extracellular milieu is considered a mode of finely controlling their

    更新日期:2020-03-30
  • Myeloid-Derived Suppressor Cells as Target of Phosphodiesterase-5 Inhibitors in Host-Directed Therapeutics for Tuberculosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-27
    Vinzeigh Leukes; Gerhard Walzl; Nelita du Plessis

    Resistance toward current and new classes of anti-tuberculosis (anti-TB) antibiotics are rapidly emerging; thus, innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for shortening therapy regimens without inducing drug resistance. Development of new TB drugs is lengthy and expensive, and success is not guaranteed; thus, alternatives

    更新日期:2020-03-30
  • Leupaxin Expression Is Dispensable for B Cell Immune Responses
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-28
    Amélie Bonaud; Simon Clare; Valeria Bisio; John M. Sowerby; Shugang Yao; Hanne Ostergaard; Karl Balabanian; Kenneth G. C. Smith; Marion Espéli

    The generation of a potent humoral immune response by B cells relies on the integration of signals induced by the B cell receptor, toll-like receptors and both negative and positive co-receptors. Several reports also suggest that integrin signaling plays an important role in this process. How integrin signaling is regulated in B cells is however still partially understood. Integrin activity and function

    更新日期:2020-03-30
  • Mononuclear Phagocyte Activation Is Associated With the Immunopathology of Psoriasis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-02
    Mariana C. Costa; Camilla S. Paixão; Débora L. Viana; Bruno de O. Rocha; Maíra Saldanha; Lícia M. H. da Mota; Paulo R. L. Machado; Carla Pagliari; Maria de Fátima de Oliveira; Sergio Arruda; Edgar M. Carvalho; Lucas P. Carvalho

    Psoriasis is a chronic, inflammatory disease affecting the skin and joints. The pathogenesis of this disease is associated with genetic, environmental and immunological factors, especially unbalanced T cell activation and improper keratinocyte differentiation. Psoriatic lesion infiltrate is composed of monocytes and T cells, and most studies have focused on the participation of T cells in the pathogenesis

    更新日期:2020-03-30
  • Engineering of Fc Multimers as a Protein Therapy for Autoimmune Disease
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-04
    Elizabeth A. Fitzpatrick; Jin Wang; S. E. Strome

    The success of Intravenous Immunoglobulin in treating autoimmune and inflammatory processes such as immune thrombocytopenia purpura and Kawasaki disease has led to renewed interest in developing recombinant molecules capable of recapitulating these therapeutic effects. The anti-inflammatory properties of IVIG are, in part, due to the Fc region of the IgG molecule, which interacts with activating or

    更新日期:2020-03-30
  • Innate Activation of IFN-γ—iNOS Axis During Infection With Salmonella Represses the Ability of T Cells to Produce IL-2
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Jitender Yadav; Neha Dikshit; Sana Ismaeel; Ayub Qadri

    Pathogenic Salmonella serovars are a major cause of enteric illness in humans and animals, and produce clinical manifestations ranging from localized gastroenteritis to systemic disease. T cells are a critical component of immunity against this intracellular pathogen. The mechanisms by which Salmonella modulates T-cell—mediated immune responses in order to establish systemic infection are not completely

    更新日期:2020-03-30
  • Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Woosuk Choi; Shawn Choe; Gee W. Lau

    Forkhead box (FOX) proteins are transcriptional factors that regulate various cellular processes. This minireview provides an overview of FOXA2 functions, with a special emphasis on the regulation airway mucus homeostasis in both healthy and diseased lungs. FOXA2 plays crucial roles during lung morphogenesis, surfactant protein production, goblet cell differentiation and mucin expression. In healthy

    更新日期:2020-03-28
  • Two Is Better Than One: Evidence for T-Cell Cross-Protection Between Dengue and Zika and Implications on Vaccine Design
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Krishanthi S. Subramaniam; Suzannah Lant; Lynsey Goodwin; Alba Grifoni; Daniela Weiskopf; Lance Turtle

    Dengue virus (DENV, family Flaviviridae, genus Flavivirus) exists as four distinct serotypes. Generally, immunity after infection with one serotype is protective and lifelong, though exceptions have been described. However, secondary infection with a different serotype can result in more severe disease for a minority of patients. Host responses to the first DENV infection involve the development of

    更新日期:2020-03-28
  • Drosophila as a Model System to Investigate the Effects of Mitochondrial Variation on Innate Immunity
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Tiina S. Salminen; Pedro F. Vale

    Understanding why the response to infection varies between individuals remains one of the major challenges in immunology and infection biology. A substantial proportion of this heterogeneity can be explained by individual genetic differences which result in variable immune responses, and there are many examples of polymorphisms in nuclear-encoded genes that alter immunocompetence. However, how immunity

    更新日期:2020-03-27
  • Dysregulated CD4+ T Cells and microRNAs in Myocarditis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-09
    Jing Wang; Bo Han

    Myocarditis is a polymorphic disease complicated with indeterminate etiology and pathogenesis, and represents one of the most challenging clinical problems lacking specific diagnosis and effective therapy. It is caused by a complex interplay of environmental and genetic factors, and causal links between dysregulated microribonucleic acids (miRNAs) and myocarditis have also been supported by recent

    更新日期:2020-03-27
  • Deep Phenotyping of Urinary Leukocytes by Mass Cytometry Reveals a Leukocyte Signature for Early and Non-Invasive Prediction of Response to Treatment in Active Lupus Nephritis
    Front. Immunol. (IF 4.716) Pub Date : 2020-01-30
    Martina Bertolo; Sabine Baumgart; Pawel Durek; Anette Peddinghaus; Henrik Mei; Thomas Rose; Philipp Enghard; Andreas Grützkau

    Non-invasive biomarkers are necessary for diagnosis and monitoring disease activity in lupus nephritis (LN) to circumvent risks and limitations of renal biopsies. To identify new non-invasive cellular biomarkers in the urine sediment of LN patients, which may reflect kidney inflammation and can be used to predict treatment outcome, we performed in-depth urinary immune cell profiling by mass cytometry

    更新日期:2020-03-27
  • Nuclear Factor κB (NF-κB)–Mediated Inflammation in Multiple Sclerosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-19
    Yifan Zhou; Chunping Cui; Xiaoyu Ma; Wenjing Luo; Song Guo Zheng; Wei Qiu

    The nuclear factor κB (NF-κB) signaling cascade has been implicating in a broad range of biological processes, including inflammation, cell proliferation, differentiation, and apoptosis. The past three decades have witnessed a great progress in understanding the impact of aberrant NF-κB regulation on human autoimmune and inflammatory disorders. In this review, we discuss how aberrant NF-κB activation

    更新日期:2020-03-27
  • Xeno-miRNA in Maternal-Infant Immune Crosstalk: An Aid to Disease Alleviation
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-20
    Bjorn John Stephen; Nidhi Pareek; Mohd Saeed; Mohd Adnan Kausar; Safikur Rahman; Manali Datta

    Human milk is a complex liquid that contains multifaceted compounds which provide nutrition to infants and helps to develop their immune system. The presence of secretory immunoglobulins (IgA), leucocytes, lysozyme, lactoferrin, etc., in breast milk and their role in imparting passive immunity to infants as well as modulating development of an infant's immune system is well-established. Breast milk

    更新日期:2020-03-27
  • Systematic Review of Safety and Efficacy of Atacicept in Treating Immune-Mediated Disorders
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-25
    Celine Kaegi; Urs C. Steiner; Benjamin Wuest; Catherine Crowley; Onur Boyman

    Background: Biological agents (also termed biologics or biologicals) play a growingly central role in the treatment of immunological diseases. However, the numerous studies published on biologics complicate the decision on the most appropriate biologic for a given disease. We aim to address this problem by publishing a series of systematic reviews evaluating the safety and efficacy of B cell-targeting

    更新日期:2020-03-27
  • The Role of B7 Family Molecules in Maternal–Fetal Immunity
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-27
    Yongbo Zhao; Qingliang Zheng; Liping Jin

    Pregnancy is a complex but well-arranged process, and a healthy fetus requires immune privilege and surveillance in the presence of paternally derived antigens. Maternal and fetal cells interact at the maternal–fetal interface. The upregulation and downregulation of maternal immunity executed by the leukocyte population predominantly depend on the activity of decidual natural killer cells and trophoblasts

    更新日期:2020-03-27
  • Optimization of Organotypic Cultures of Mouse Spleen for Staining and Functional Assays
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-28
    Francesca Finetti; Nagaja Capitani; Noemi Manganaro; Vanessa Tatangelo; Francesca Libonati; Giulia Panattoni; Ivo Calaresu; Laura Ballerini; Cosima T. Baldari; Laura Patrussi

    By preserving cell viability and three-dimensional localization, organotypic culture stands out among the newest frontiers of cell culture. It has been successfully employed for the study of diseases among which neoplasias, where tumoral cells take advantage of the surrounding stroma to promote their own proliferation and survival. Organotypic culture acquires major importance in the context of the

    更新日期:2020-03-26
  • Escape or Fight: Inhibitors in Hemophilia A
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-02
    Simone Merlin; Antonia Follenzi

    Replacement therapy with coagulation factor VIII (FVIII) represents the current clinical treatment for patients affected by hemophilia A (HA). This treatment while effective is, however, hampered by the formation of antibodies which inhibit the activity of infused FVIII in up to 30% of treated patients. Immune tolerance induction (ITI) protocols, which envisage frequent infusions of high doses of FVIII

    更新日期:2020-03-24
  • Rapid Induction and Maintenance of Virus-Specific CD8+ TEMRA and CD4+ TEM Cells Following Protective Vaccination Against Dengue Virus Challenge in Humans
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-02
    Nancy Graham; Phil Eisenhauer; Sean A. Diehl; Kristen K. Pierce; Stephen S. Whitehead; Anna P. Durbin; Beth D. Kirkpatrick; Alessandro Sette; Daniela Weiskopf; Jonathan E. Boyson; Jason W. Botten

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease. The current lack of an effective vaccine to simultaneously protect against the four serotypes of DENV in seronegative individuals is a major unmet medical need. Further, the immunological basis for protective immunity in the setting of DENV infection or vaccination is not fully understood. Our team has developed a

    更新日期:2020-03-24
  • Infant Alveolar Macrophages Are Unable to Effectively Contain Mycobacterium tuberculosis
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-03
    Anu Goenka; Ian E. Prise; Emma Connolly; Paulina Fernandez-Soto; David Morgan; Jennifer S. Cavet; John R. Grainger; Jaya Nichani; Peter D. Arkwright; Tracy Hussell

    Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant alveolar macrophages (AMϕs) compared with those of adults. We develop a method of obtaining AMϕs from healthy infants using rigid bronchoscopy and incubate

    更新日期:2020-03-24
  • The Role of PD-1 in Acute and Chronic Infection
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-03
    Jil M. Jubel; Zachary R. Barbati; Christof Burger; Dieter C. Wirtz; Frank A. Schildberg

    PD-1 as an immune checkpoint molecule down-regulates T cell activity during immune responses in order to prevent autoimmune tissue damage. In chronic infections or tumors, lasting antigen-exposure leads to permanent PD-1 expression that can limit immune-mediated clearance of pathogens or degenerated cells. Blocking PD-1 can enhance T cell function; in cancer treatment PD-1 blockade is already used

    更新日期:2020-03-24
  • Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-03
    Paolo Casali; Tian Shen; Yijiang Xu; Zhifang Qiu; Daniel P. Chupp; John Im; Zhenming Xu; Hong Zan

    Estrogen contributes to females' strong antibody response to microbial vaccines and proneness to autoimmunity, particularly antibody-mediated systemic autoimmunity, in females. We have hypothesized that this is due to estrogen-mediated potentiation of class switch DNA recombination (CSR) and somatic hypermutation (SHM). As we have shown, estrogen boosts AID expression, which is critical for both CSR

    更新日期:2020-03-24
  • Targeting ADAM10 in Cancer and Autoimmunity
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-04
    Timothy M. Smith; Anuj Tharakan; Rebecca K. Martin

    Generating inhibitors for ADisintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating significant data, yet the clinical trials have not replicated the same results. ADAM10 is ubiquitously expressed

    更新日期:2020-03-24
  • Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-06
    Thomas N. Wight; Inkyung Kang; Stephen P. Evanko; Ingrid A. Harten; Mary Y. Chang; Oliver M. T. Pearce; Carys E. Allen; Charles W. Frevert

    The extracellular matrix (ECM) proteoglycan, versican increases along with other ECM versican binding molecules such as hyaluronan, tumor necrosis factor stimulated gene-6 (TSG-6), and inter alpha trypsin inhibitor (IαI) during inflammation in a number of different diseases such as cardiovascular and lung disease, autoimmune diseases, and several different cancers. These interactions form stable scaffolds

    更新日期:2020-03-24
  • The Emerging Roles of NDR1/2 in Infection and Inflammation
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-09
    Xiaolan Ye; Naomi Ong; Huazhang An; Yuejuan Zheng

    The nuclear Dbf2-related (NDR) kinases NDR1 and NDR2 belong to the NDR/LATS (large tumor suppressor) subfamily in the Hippo signaling pathway. They are highly conserved from yeast to humans. It is well-known that NDR1/2 control important cellular processes, such as morphological changes, centrosome duplication, cell proliferation, and apoptosis. Recent studies revealed that NDR1/2 also play important

    更新日期:2020-03-24
  • Preventing Infections by Encapsulated Bacteria Through Vaccine Prophylaxis in Inflammatory Bowel Disease
    Front. Immunol. (IF 4.716) Pub Date : 2020-03-03
    Marco Vincenzo Lenti; Caterina Mengoli; Marta Vernero; Nicola Aronico; Laura Conti; Federica Borrelli de Andreis; Sara Cococcia; Antonio Di Sabatino

    Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn's disease, is an immune-mediated, chronic-relapsing, disabling disorder which is associated with increased mortality and poor patients' quality of life. Patients with IBD are at increased risk of infections for many reasons. In fact, IBD often requires a lifelong immunosuppressive and/or biologic therapy, both commonly associated

    更新日期:2020-03-24
  • Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-07
    Manuel O. Jakob; Shaira Murugan; Christoph S. N. Klose

    The dense innervation of the gastro-intestinal tract with neuronal networks, which are in close proximity to immune cells, implies a pivotal role of neurons in modulating immune functions. Neurons have the ability to directly sense danger signals, adapt immune effector functions and integrate these signals to maintain tissue integrity and host defense strategies. The expression pattern of a large set

    更新日期:2020-03-24
  • Microglia in Multiple Sclerosis: Friend or Foe?
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-17
    Brooke L. Guerrero; Nancy L. Sicotte

    Microglia originate from myeloid progenitors in the embryonic yolk sac and play an integral role in central nervous system (CNS) development, immune surveillance and repair. The role of microglia in multiple sclerosis (MS) has been complex and controversial, with evidence suggesting that these cells play key roles in both active inflammation and remyelination. Here we will review the most recent histological

    更新日期:2020-03-24
  • Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)
    Front. Immunol. (IF 4.716) Pub Date : 2020-02-18
    Anu Kauppinen; Kai Kaarniranta; Antero Salminen

    Myeloid cells, such as granulocytes/neutrophils and macrophages, have responsibilities that include pathogen destruction, waste material degradation, or antigen presentation upon inflammation. During persistent stress, myeloid cells can remain partially differentiated and adopt immunosuppressive functions. Myeloid-derived suppressor cells (MDSCs) are primarily beneficial upon restoring homeostasis

    更新日期:2020-03-22
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