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Development of a C3 humanized rat as a new model for evaluating novel C3 inhibitors. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-30 Jin Chen,Lingjun Zhang,Maojing Yang,Elizabeth D Hughes,Zach Freeman,Thomas L Saunders,Feng Lin
INTRODUCTION C3 is central for all complement activation pathways, thus an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or non-human primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. METHODS We
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Metabolism shapes immune responses to Staphylococcus aureus. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-28 Prabhakar Arumugam,Tammy Kielian
Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional
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Association of Vitamin D with severity and outcome of COVID-19: Clinical and Experimental Evidence. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-26 Georgios Renieris,Spyros Foutadakis,Theano Andriopoulou,Victoria-Marina Spanou,Dionysia-Eirini Droggiti,Dionysios Kafousopoulos,Theologia Gkavogianni,Georgia Damoraki,Giannis Vatsellas,Evangelos J Giamarellos-Bourboulis
INTRODUCTION The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. METHODS 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients
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Basic Mechanisms of Immunometabolites in Shaping the Immune Response. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-23 Dylan Gerard Ryan,Christian Graham Peace,Alexander Hooftman
Background Innate immune cells play a crucial role in responding to microbial infections, but their improper activation can also drive inflammatory disease. For this reason, their activation state is governed by a multitude of factors, including the metabolic state of the cell and, more specifically, the individual metabolites which accumulate intra- and extra-cellularly. This relationship is bidirectional
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Advanced Glycation End Products-induced Activation of Keratinocytes: a Mechanism Underlying Cutaneous Immune Response in Psoriasis. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-21 Pan Kang,Jianru Chen,Shiyu Wang,Shaolong Zhang,Shuli Li,Sen Guo,Pu Song,Ling Liu,Gang Wang,Tianwen Gao,Weigang Zhang,Chunying Li
Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis via acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed increased
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Human monocytes exposed to SARS-CoV-2 display features of innate immune memory producing high levels of CXCL10 upon restimulation. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-21 Jelena Cvetkovic,Ronald H J Jacobi,Alberto Miranda-Bedate,Nhung Pham,Martina Kutmon,James Groot,Martijn D B van de Garde,Elena Pinelli
Introduction A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether SARS-CoV-2 can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes. Methods Monocytes were exposed to inactivated (i)SARS-CoV-2 for 24 hours, followed
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Human Ribonuclease 6 has a Protective Role During Experimental Urinary Tract Infection. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-18 Juan de Dios Ruiz-Rosado,Hanna Cortado,Macie Kercsmar,Birong Li,Gregory Ballash,Israel Cotzomi-Ortega,Yuriko I Sanchez-Zamora,Sudipti Gupta,Christina Ching,Ester Boix,Ashley R Jackson,John David Spencer,Brian Becknell
Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated
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Functional analysis of a novel complement C5a receptor 1-blocking monoclonal antibody. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-10 Leon Cyranka,Ida Mariegaard,Mikkel-Ole Skjødt,Rafael Bayarri-Olmos,Tom Eirik Mollnes,Peter Garred,Anne Rosbjerg
Introduction The complement system anaphylatoxin C5a is a critical player in inflammation. By binding to complement C5a receptor 1 (C5aR1/CD88), C5a regulates many cellular functions, mainly as a potent pro-inflammatory inducer, such as cytokine release, cellular motility, and homeostasis. We describe the generation and selection of a potent antagonistic C5aR1 mouse monoclonal antibody (mAb). Methods
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Immunothrombosis and complement activation contribute to disease severity and adverse outcome in COVID-19. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-08 Tiphaine Ruggeri,Yasmin De Wit,Noëlia Schärz,Gerard van Mierlo,Anne Angelillo-Scherrer,Justine Brodard,Joerg Schefold,Cédric Hirzel,Ilse Jongerius,Sacha Zeerleder
Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement - and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum
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Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis. J. Innate Immun. (IF 5.3) Pub Date : 2023-11-03 Yaqin Zhang,Ziying Jiao,Shanshan Wang
This study investigates whether bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can affect rheumatoid arthritis (RA) by delivering microRNA (miR)-378a-5p to regulate the IRF1/STAT1 axis. We identified RA-associated miRNAs using GEO microarray dataset GSE121894. We found the most important miRNAs in RA synovial tissues using RT-qPCR. BMSCs-derived EVs were ultracentrifuged
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YTHDC1-modified m6A methylation of hsa_circ_0102678 promotes keratinocyte inflammation induced by Cutibacterium acnes biofilm through regulating miR-146a/TRAF6 and IRAK1 axis. J. Innate Immun. (IF 5.3) Pub Date : 2023-10-30 Meng Zhou,Yuzhen Liu,Haoxiang Xu,Xu Chen,Nana Zheng,Zhimin Duan,Yiping Ge,Dongqing Li,Tong Lin,Rong Zeng,Qing Chen,Min Li
INTRODUCTION CircRNAs are closely related to many human diseases, however, their role in acne remains unclear. This study aimed to determine the role of hsa-circ_0102678 in regulating inflammation of acne. METHODS Firstly, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and FISH assay were utilized to confirm the characteristics of
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N6-methyladenosine (m6A) modification in Natural immune cell-mediated inflammatory diseases. J. Innate Immun. (IF 5.3) Pub Date : 2023-10-30 Yan Teng,Jin Yi,Junnian Chen,Lu Yang
The post-transcriptional N6-methyladenosine (m6A) modification of RNA influences stability, transport and translation with implications for various physiological and pathological processes. Immune cell development, differentiation and activation are also thought to be regulated by m6A and affect host defense against pathogens and inflammatory response with impacts on infectious, neoplastic, autoimmune
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The intersection between bacterial metabolism and innate immunity. J. Innate Immun. (IF 5.3) Pub Date : 2023-10-27 Ivan C Acosta,Francis Alonzo
BACKGROUND The innate immune system is the first line of defense against microbial pathogens and is essential for maintaining good health. If pathogens breach innate barriers, the likelihood of infection is significantly increased. Many bacterial pathogens pose a threat to human health on account of their ability to evade innate immunity and survive in growth-restricted environments. These pathogens
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Mesenchymal Stromal Cells Facilitate Neutrophil Trained Immunity by Reprogramming Hematopoietic Stem Cells. J. Innate Immun. (IF 5.3) Pub Date : 2023-10-05 Julie Ng,Anna E Marneth,Alec Griffith,Daniel Younger,Sailaja Ghanta,Alan Jiao,Gareth Willis,Junwen Han,Jewel Imani,Bailin Niu,Joshua W Keegan,Brandon Hancock,Fei Guo,Yang Shi,Mark A Perrella,James A Lederer
Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor
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Emerging roles of cGAS-STING signaling in mediating ocular inflammation. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-30 Linbin Zhou,Bo Man Ho,Hoi Ying Emily Chan,Yan Tong,Lin Du,Jing Na He,Danny Siu-Chun Ng,Clement C Tham,Chi Pui Pang,Wai Kit Chu
Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STING). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune
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Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-23 Lei Wang,Jiaxin Lin,Kaiyan Yang,Weina Wang,Yan Lv,Xiangkang Zeng,Yaya Zhao,Junjing Yu,Lei Pan
Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the
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Selected β-glucans act as immune-training agents by improving anti-mycobacterial activity in human macrophages - a pilot study. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-21 Clara Braian,Lovisa Karlsson,Jyotirmoy Das,Maria Lerm
Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity, leads to an enhanced host response to a secondary infection. β-glucans are structural components of plants, algae, fungi and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucans curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich
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Inhibition of Piezo1 ameliorates intestinal inflammation and limits the activation of group 3 innate lymphoid cells in experimental colitis. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-19 Chang Liu,Yanan Xia,Shichen Fu,Fanyi Meng,Bingcheng Feng,Leiqi Xu,Lixiang Li,Xiuli Zuo
Piezo1, the mechanosensory ion channel, has attracted increasing attention for its essential roles in various inflammatory responses and immune-related diseases. Although most of the key immune cells in inflammatory bowel disease (IBD) have been reported to be regulated by Piezo1, the specific role of Piezo1 in colitis has yet to be intensively studied. The present study investigated the impact of
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C-terminal PEGylation improves SAAP-148 peptide's immunomodulatory activities. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-19 Miriam E Van Gent,Bep Schonkeren-Ravensbergen,Asma Achkif,Daan Beentjes,Natasja Dolezal,Krista E Van Meijgaarden,Jan Wouter Drijfhout,Peter H Nibbering
Synthetic antibacterial and anti-biofilm peptide (SAAP)-148 was developed to combat bacterial infections not effectively treatable with current antibiotics. SAAP-148 is highly effective against antimicrobial-resistant (AMR) bacteria without inducing resistance, however challenges for further development of SAAP-148 include its cytotoxicity and short circulation half-life. To circumvent these drawbacks
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Mitochondrial Damage-Associated Molecular Patterns and Metabolism in the Regulation of Innate Immunity. J. Innate Immun. (IF 5.3) Pub Date : 2023-09-04 Yanmin Lyu,Tianyu Wang,Shuhong Huang,Zhaoqiang Zhang
The innate immune system, as the host's first line of defense against intruders, plays a critical role in recognizing, identifying, and reacting to a wide range of microbial intruders. There is increasing evidence that mitochondrial stress is a major initiator of innate immune responses. When mitochondria's integrity is disrupted or dysfunction occurs, the mitochondria's contents are released into
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MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1. J. Innate Immun. (IF 5.3) Pub Date : 2023-08-22 Gayan Bamunuarachchi,Kishore Vaddadi,Xiaoyun Yang,Quanjin Dang,Zhengyu Zhu,Sankha Hewawasam,Chaoqun Huang,Yurong Liang,Yujie Guo,Lin Liu
An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase1 (TNKS1) and the endogenous small noncoding RNA, miR-9-1 in influenza A virus
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TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis. J. Innate Immun. (IF 5.3) Pub Date : 2023-08-14 Ewelina D Hejenkowska,Nilay Mitash,Joshua E Donovan,Anvita Chandra,Carol Bertrand,Chiara De Santi,Catherine M Greene,Fangping Mu,Agnieszka Swiatecka-Urban
SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher
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Pro-inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis. J. Innate Immun. (IF 5.3) Pub Date : 2023-06-29 Qingsong Zhao,Nan Xia,Jinmei Xu,Yingnan Wang,Luwen Feng,Dihan Su,Zhifeng Cheng
PR domain containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy
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Phenotypic characterization of acoustically enriched extracellular vesicles from pathogen-activated platelets. J. Innate Immun. (IF 5.3) Pub Date : 2023-05-27 Frida Palm,Axel Broman,Genevieve Marcoux,John W Semple,Thomas L Laurell,Johan Malmström,Oonagh Shannon
Extracellular vesicles (EVs) are derived from the membrane of platelets and released in the circulation upon activation or injury. Analogous to the parent cell, platelet derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increases in several pathological inflammatory diseases, such as sepsis
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Regulation of macrophage cell surface GAPDH alters LL-37 internalization and downstream effects in the cell J. Innate Immun. (IF 5.3) Pub Date : 2023-04-20 Asmita Dhiman, Sharmila Talukdar, Gaurav Kumar Chaubey, Rahul Dilawari, Radheshyam Modanwal, Surbhi Chaudhary, Anil Patidar, Vishant Mahendra Boradia, Pradeep Kumbhar, Chaaya Iyengar Raje, Manoj Raje
Mycobacterium tuberculosis (M.tb), the major causative agent of tuberculosis (TB), has evolved mechanisms to evade host defenses and persist within host cells. Host directed therapies (HDTs) against infected cells are emerging as an effective option. Cationic host defense peptide LL-37 is known to internalize into cells and induce autophagy resulting in intracellular killing of M.tb. This peptide also
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Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction J. Innate Immun. (IF 5.3) Pub Date : 2023-04-17 Jianmin Chen, Shani Austin-Williams, Caroline Elizabeth O'Riordan, Pol Claria-Ribas, Michelle A Sugimoto, Lucy V Norling, Christoph Thiemermann, Mauro Perretti
Using a global formyl-peptide receptor (Fpr)2 knockout mouse colony, we have reported the modulatory properties of this pro-resolving receptor in polymicrobial sepsis. Herein, we have used a humanized FPR2 (hFPR2) mouse colony bearing an intact or a selective receptor deficiency in myeloid cells to dwell on the cellular mechanisms. hFPR2 mice and myeloid cell-specific hFPR2 KO (abbreviated to KO) mice
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TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment J. Innate Immun. (IF 5.3) Pub Date : 2023-04-11 Miriam Simón-Fuentes, Cristina Herrero, Lucia Acero-Riaguas, Concha Nieto, Fatima Lasala, Nuria Labiod, Joanna Luczkowiak, Bárbara Alonso, Rafael Delgado, Maria Colmenares, Ángel L. Corbí, Ángeles Domínguez-Soto
Toll-like receptor 7 (TLR7) is an endosomal Pathogen-Associated Molecular Pattern (PAMP) receptor that senses single-stranded RNA (ssRNA) and whose engagement results in the production of type I IFN and pro-inflammatory cytokines upon viral exposure. Recent genetic studies have established that a dysfunctional TLR7-initiated signaling is directly linked to the development of inflammatory responses
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Interactions between macrophages and biofilm during Staphylococcus aureus-associated implant infection: difficulties and solutions J. Innate Immun. (IF 5.3) Pub Date : 2023-04-03 Mingzhang Li, Jinlong Yu, Geyong Guo, Hao Shen
Staphylococcus aureus (S. aureus) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. Planktonic S. aureus attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances (EPS), forming a solid and complex biofilm. This provides a stable environment
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Single Cell Analysis of the Fate of Injected Oncogenic RasV12 Cells in Adult Wild Type Drosophila J. Innate Immun. (IF 5.3) Pub Date : 2023-03-30 Di Chen, Xiao Lan, Xiaoming Huang, Jieqing Huang, Xiaojing Zhou, Zhichao Miao, Yuting Ma, Akira Goto, Shanming Ji, Jules A. Hoffmann
We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the
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Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology J. Innate Immun. (IF 5.3) Pub Date : 2023-03-25 Melissa Thaler, Ying Wang, Anne M. van der Does, Alen Faiz, Dennis K. Ninaber, Natacha S. Ogando, Hendrik Beckert, Christian Taube, Clarisse Salgado-Benvindo, Eric J. Snijder, Peter J. Bredenbeek, Pieter S. Hiemstra, Martijn J. van Hemert
The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface
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Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis J. Innate Immun. (IF 5.3) Pub Date : 2023-03-21 Luxi Zou, Ling Sun, Ruixue Hua, Yu Wu, Linlin Sun, Ting Chen
The correlation between ubiquitin-editing enzyme A20 and E3 ubiquitin ligase ring finger protein (RNF) 168 has been reported to be critical for repair of DNA damage. This study aimed to evaluate the potential role of this regulatory interaction in the pathogenesis of lupus nephritis (LN). The expression of RNF168 and A20 was measured in the podocytes derived from MRL/lpr murine lupus as well as patients
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IL-33 ameliorates murine systemic lupus erythematosus and is associated with induction of M2 macrophage polarisation and regulatory T cells J. Innate Immun. (IF 5.3) Pub Date : 2023-03-08 Mo Yin Mok, Ka Sin Law, Wing Yin Kong, Cai Yun Luo, Endale T Asfaw, Kwok Wah Chan, Fang Ping Huang, Chak Sing Lau, Godfrey Chi Fung Chan
The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone
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Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages J. Innate Immun. (IF 5.3) Pub Date : 2023-03-07 Kai-Chen Wu, Nicholas D Condon, Timothy A. Hill, Robert C. Reid, David Fairlie, Junxian Lim
Complement activation and Rab GTPase trafficking are commonly observed in inflammatory responses. Recruitment of innate immune cells to sites of infection or injury and secretion of inflammatory chemokines are promoted by complement component 5a (C5a) that activates the cell surface protein C5a receptor1 (C5aR1). Persistent activation can lead to a myriad of inflammatory and autoimmune diseases. Here
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Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance? J. Innate Immun. (IF 5.3) Pub Date : 2023-03-01 Marco Mannes, Rebecca Halbgebauer, Lisa Wohlgemuth, David Alexander Christian Messerer, Susa Savukoski, Anke Schultze, Bettina Berger, Christiane Leonie Knapp, Christoph Q. Schmidt, Daniel Fürst, Morten Hillmer, Reiner Siebert, Oskar Eriksson, Barbro Persson, Bo Nilsson, Kristina Nilsson Ekdahl, Markus Huber-Lang
The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625Cgt;T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with
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Tryptophol acetate and tyrosol acetate, small molecule metabolites identified in a probiotic mixture, inhibit hyperinflammation J. Innate Immun. (IF 5.3) Pub Date : 2023-02-21
Probiotic fermented foods are perceived as contributing to human health, however solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus inhibit hyperinflammation (e.g., “cytokine storm”). Comprehensive in vivo
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Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating Natural Killer Cell Survival J. Innate Immun. (IF 5.3) Pub Date : 2023-01-19 Fábio S.Y. Yoshikawa, Maki Wakatsuki, Kosuke Yoshida, Rikio Yabe, Shota Torigoe, Sho Yamasaki, Glen N. Barber, Shinobu Saijo
Aspergillus fumigatus is a ubiquitous, yet potentially pathogenic, mold. The immune system employs innate receptors, such as dectin-1, to recognize fungal pathogens, but the immunological networks that afford protection are poorly explored. Here, we investigated the role of dectin-1 in anti-A. fumigatus response in an experimental model of acute invasive aspergillosis. Mice lacking dectin-1 presented
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Ste20-Like Kinase TAOK1 Positively Regulates Antiviral Responses by Controlling the TBK1-IRF3 Signaling Axis J. Innate Immun. (IF 5.3) Pub Date : 2023-01-17 Xiaogang Luo, Ruihua Ji, Qianru Liu, Xiaoxue Xiao, Wengang Song, Huazhang An, Yingke Li, Jun Zhou
The cytosolic viral nucleic acid-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor interferon (IFN)-regulatory factor 3 (IRF3) to induce type I IFN production and antiviral immune responses. However, the mechanism that triggers the binding of TBK1 and IRF3 after virus infection remains not fully understood. Here, we identified that thousand and
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Serine Protease Networks Mediate Immune Responses in Extra-Embryonic Tissues of Eggs in the Tobacco Hornworm, Manduca sexta J. Innate Immun. (IF 5.3) Pub Date : 2022-12-13 Tisheng Shan, Yang Wang, Neal T. Dittmer, Michael R. Kanost, Haobo Jiang
The melanization and Toll pathways, regulated by a network of serine proteases and noncatalytic serine protease homologs (SPHs), have been investigated mostly in adult and larval insects. However, how these innate immune reactions are regulated in insect eggs remains unclear. Here we present evidence from transcriptome and proteome analyses that extra-embryonic tissues (yolk and serosa) of early-stage
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Acknowledgement to Reviewers J. Innate Immun. (IF 5.3) Pub Date : 2022-12-07
J Innate Immun 2022;14:690–691
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Farewell to Professors Arne Egesten and Heiko Herwald J. Innate Immun. (IF 5.3) Pub Date : 2022-12-06
J Innate Immun 2022;14:1
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Interference with Lipoprotein Maturation Sensitizes Methicillin-Resistant Staphylococcus aureus to Human Group IIA-Secreted Phospholipase A2 and Daptomycin J. Innate Immun. (IF 5.3) Pub Date : 2022-12-06 Marieke M. Kuijk, Yongzheng Wu, Vincent P. van Hensbergen, Gizem Shanlitourk, Christine Payré, Gérard Lambeau, Sandra Man-Bovenkerk, Jennifer Herrmann, Rolf Müller, Jos A.G. van Strijp, Yvonne Pannekoek, Lhousseine Touqui, Nina M. van Sorge
Methicillin-resistant Staphylococcus aureus (MRSA) has been classified as a high priority pathogen by the World Health Organization underlining the high demand for new therapeutics to treat infections. Human group IIA-secreted phospholipase A2 (hGIIA) is among the most potent bactericidal proteins against Gram-positive bacteria, including S. aureus. To determine hGIIA-resistance mechanisms of MRSA
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The Olfactomedin-4-Defined Human Neutrophil Subsets Differ in Proteomic Profile in Healthy Individuals and Patients with Septic Shock J. Innate Immun. (IF 5.3) Pub Date : 2022-11-30
The specific granule glycoprotein olfactomedin-4 (Olfm4) marks a subset (1–70%) of human neutrophils and the Olfm4-high (Olfm4-H) proportion has been found to correlate with septic shock severity. The aim of this study was to decipher proteomic differences between the subsets in healthy individuals, hypothesizing that Olfm4-H neutrophils have a proteomic profile distinct from that of Olfm4 low (Olfm4-L)
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CLIPA7 Exhibits Pleiotropic Roles in the Anopheles gambiae Immune Response J. Innate Immun. (IF 5.3) Pub Date : 2022-11-24
Clip domain serine proteases and clip domain serine protease homologs (cSPHs) are key components of serine protease cascades that drive the melanization response. Despite lacking catalytic activity, cSPHs play essential roles in regulating melanization, but the spectrum of functions they catalyze within and outside these cascades is not fully understood. Aside from their classical role as cofactors
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IRF1 Is Required for MDA5 (IFIH1) Induction by IFN-α, LPS, and poly(I:C) in Murine Macrophages J. Innate Immun. (IF 5.3) Pub Date : 2022-11-15 Iris Aparici-Herraiz, Guillem Sánchez-Sánchez, Carlos Batlle, Pere Rehues, Martí López-Serrat, Lorena Valverde-Estrella, Jorge Lloberas, Antonio Celada
Melanoma differentiation-associated protein 5 (MDA5) induces type I interferons (IFNs) after the recognition of viral RNA. In addition, gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene, which encodes MDA5, lead to type I interferonopathies. Here, we show that Mda5 is highly expressed in murine macrophages and is regulated by pro-inflammatory stimuli such as
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GSK3β Inhibition Prevents Macrophage Reprogramming by High-Dose Methotrexate J. Innate Immun. (IF 5.3) Pub Date : 2022-11-14 Israel Ríos, Baltasar López-Navarro, Mónica Torres-Torresano, Blanca Soler Palacios, Miriam Simón-Fuentes, Ángeles Domínguez-Soto, Ittai B. Muller, Gerrit Jansen, Ángel L. Corbí, Amaya Puig-Kröger
Methotrexate (MTX) is an antifolate drug used as a chemotherapeutic agent for acute lymphoblastic leukemia, where MTX improves patients’ prognosis. Macrophage reprogramming is being increasingly assessed as an antitumor therapeutic strategy. However, and although MTX limits the pathogenic action of macrophages in chronic inflammatory diseases, its effects on tumor-promoting macrophages have not been
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MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury J. Innate Immun. (IF 5.3) Pub Date : 2022-10-21 Jian Lin, Zhanjun Lu, Gengfeng Li, Cui Zhang, Huiying Lu, Sheng Gao, Ruixin Zhu, Hailiang Huang, Konrad Aden, Jianhua Wang, Yingzi Cong, Huili Wu, Zhanju Liu
Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury
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MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury J. Innate Immun. (IF 5.3) Pub Date : 2022-10-21
Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury
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Obesity Exacerbates Lupus Activity in Fc Gamma Receptor IIb Deficient Lupus Mice Partly through Saturated Fatty Acid-Induced Gut Barrier Defect and Systemic Inflammation J. Innate Immun. (IF 5.3) Pub Date : 2022-10-11 Kanyarat Udompornpitak, Awirut Charoensappakit, Kritsanawan Sae-Khow, Thansita Bhunyakarnjanarat, Cong Phi Dang, Wilasinee Saisorn, Peerapat Visitchanakun, Pornpimol Phuengmaung, Tanapat Palaga, Patcharee Ritprajak, Somkanya Tungsanga, Asada Leelahavanichkul
The prevalence of obesity is increasing, and the coexistence of obesity and systemic lupus erythematosus (lupus) is possible. A high-fat diet (HFD) was orally administered for 6 months in female 8-week-old Fc gamma receptor IIb deficient (FcgRIIb−/−) lupus or age and gender-matched wild-type (WT) mice. Lupus nephritis (anti-dsDNA, proteinuria, and increased creatinine), gut barrier defect (fluorescein
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Obesity Exacerbates Lupus Activity in Fc Gamma Receptor IIb Deficient Lupus Mice Partly through Saturated Fatty Acid-Induced Gut Barrier Defect and Systemic Inflammation J. Innate Immun. (IF 5.3) Pub Date : 2022-10-11
The prevalence of obesity is increasing, and the coexistence of obesity and systemic lupus erythematosus (lupus) is possible. A high-fat diet (HFD) was orally administered for 6 months in female 8-week-old Fc gamma receptor IIb deficient (FcgRIIb−/−) lupus or age and gender-matched wild-type (WT) mice. Lupus nephritis (anti-dsDNA, proteinuria, and increased creatinine), gut barrier defect (fluorescein
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Ovalbumin-Induced Epithelial Activation Directs Monocyte-Derived Dendritic Cells to Instruct Type 2 Inflammation in T Cells Which Is Differentially Modulated by 2′-Fucosyllactose and 3-Fucosyllactose J. Innate Immun. (IF 5.3) Pub Date : 2022-10-10 Marit Zuurveld, Pien C.J. Kiliaan, Sophie E.L. van Grinsven, Gert Folkerts, Johan Garssen, Belinda van’t Land, Linette E.M. Willemsen
Allergic sensitization starts with epithelial cell activation driving dendritic cells (DCs) to instruct T helper 2 (Th2) cell polarization. Food allergens trigger intestinal epithelial cell (IEC) activation. Human milk oligosaccharides may temper the allergic phenotype by shaping mucosal immune responses.We investigated in vitro mucosal immune development after allergen exposure by combining ovalbumin
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Ovalbumin-Induced Epithelial Activation Directs Monocyte-Derived Dendritic Cells to Instruct Type 2 Inflammation in T Cells Which Is Differentially Modulated by 2′-Fucosyllactose and 3-Fucosyllactose J. Innate Immun. (IF 5.3) Pub Date : 2022-10-10
Allergic sensitization starts with epithelial cell activation driving dendritic cells (DCs) to instruct T helper 2 (Th2) cell polarization. Food allergens trigger intestinal epithelial cell (IEC) activation. Human milk oligosaccharides may temper the allergic phenotype by shaping mucosal immune responses.We investigated in vitro mucosal immune development after allergen exposure by combining ovalbumin
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Cathelicidins Induce Toll-Interacting Protein Synthesis to Prevent Apoptosis in Colonic Epithelium J. Innate Immun. (IF 5.3) Pub Date : 2022-09-16 Ravi Holani, Chathurika Rathnayaka, Graham A.D. Blyth, Anshu Babbar, Priyoshi Lahiri, Daniel Young, Antoine Dufour, Morley D. Hollenberg, Derek M. McKay, Eduardo R. Cobo
Cathelicidin peptides secreted by leukocytes and epithelial cells are microbicidal but also regulate pathogen sensing via toll-like receptors (TLRs) in the colon by mechanisms that are not fully understood. Herein, analyses with the attaching/effacing pathogen Citrobacter rodentium model of colitis in cathelicidin-deficient (Camp−/−) mice, and colonic epithelia demonstrate that cathelicidins prevent
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Cathelicidins Induce Toll-Interacting Protein Synthesis to Prevent Apoptosis in Colonic Epithelium J. Innate Immun. (IF 5.3) Pub Date : 2022-09-16
Cathelicidin peptides secreted by leukocytes and epithelial cells are microbicidal but also regulate pathogen sensing via toll-like receptors (TLRs) in the colon by mechanisms that are not fully understood. Herein, analyses with the attaching/effacing pathogen Citrobacter rodentium model of colitis in cathelicidin-deficient (Camp−/−) mice, and colonic epithelia demonstrate that cathelicidins prevent
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Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease J. Innate Immun. (IF 5.3) Pub Date : 2022-08-23 Michiko Mori, Carl-Magnus Clausson, Caroline Sanden, Jimmie Jönsson, Cecilia K. Andersson, Premkumar Siddhuraj, Medya Shikhagaie, Karolina Åkesson, Anders Bergqvist, Claes-Göran Löfdahl, Jonas S. Erjefält
Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex
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Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease J. Innate Immun. (IF 5.3) Pub Date : 2022-08-23
Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex
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Ex vivo and in vitro Monocyte Responses Do Not Reflect in vivo Immune Responses and Tolerance J. Innate Immun. (IF 5.3) Pub Date : 2022-08-08 Aron Jansen, Niklas Bruse, Nicole Waalders, Jelle Gerretsen, Daniëlle Rijbroek, Peter Pickkers, Matthijs Kox
Cytokine production by ex vivo (EV)-stimulated leukocytes is commonly used to gauge immune function and frequently proposed to guide immunomodulatory therapy. However, whether EV cytokine production capacity accurately reflects the in vivo (IV) immune status is largely unknown. We investigated relationships between EV monocyte cytokine responses and IV cytokine responses in a large cohort of healthy
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Ex vivo and in vitro Monocyte Responses Do Not Reflect in vivo Immune Responses and Tolerance J. Innate Immun. (IF 5.3) Pub Date : 2022-08-08
Cytokine production by ex vivo (EV)-stimulated leukocytes is commonly used to gauge immune function and frequently proposed to guide immunomodulatory therapy. However, whether EV cytokine production capacity accurately reflects the in vivo (IV) immune status is largely unknown. We investigated relationships between EV monocyte cytokine responses and IV cytokine responses in a large cohort of healthy
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Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil’s Antimicrobial Response by Engaging the Histamine 2 Receptor J. Innate Immun. (IF 5.3) Pub Date : 2022-07-20 Karim Dib, Amal El Banna, Clara Radulescu, Guillermo Lopez Campos, Gerard Sheehan, Kevin Kavanagh
We found that histamine (10−9 M) did not have any effect on the in vitro capture of Escherichia coli by neutrophils but accelerated its intracellular killing. In contrast, histamine (10−6 M) delayed the capture of Escherichia coli by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H4R and the H2R, which are coupled to the
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Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil’s Antimicrobial Response by Engaging the Histamine 2 Receptor J. Innate Immun. (IF 5.3) Pub Date : 2022-07-20
We found that histamine (10−9 M) did not have any effect on the in vitro capture of Escherichia coli by neutrophils but accelerated its intracellular killing. In contrast, histamine (10−6 M) delayed the capture of Escherichia coli by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H4R and the H2R, which are coupled to the
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Procoagulant Activity of Blood and Microvesicles Is Disturbed by Pneumococcal Pneumolysin, Which Interacts with Coagulation Factors J. Innate Immun. (IF 5.3) Pub Date : 2022-07-15 Sonja Oehmcke-Hecht, Claudia Maletzki, Surabhi Surabhi, Nikolai Siemens, Valeria Khaimov, Lisa Marie John, Sina Mariella Peter, Sven Hammerschmidt, Bernd Kreikemeyer
The coagulation and contact systems are parts of the innate immune system as they prevent bleeding and dissemination of pathogens and also contribute to microbial killing by inflammatory reactions and the release of antimicrobial peptides. Here, we investigated the influence of Streptococcus pneumoniae on the coagulation and contact system. S. pneumoniae (pneumococci), but no other investigated streptococcal