DOCSLIB.ORG

Pathway in Gastric Epithelial Cells IL-8 Secretion Via the TLR4

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pathway in Gastric Epithelial Cells IL-8 Secretion Via the TLR4 The C-Terminal Disulfide Bonds of Helicobacter pylori GroES Are Critical for IL-8 Secretion via the TLR4-Dependent Pathway in Gastric Epithelial Cells This information is current as of September 26, 2021. Yu-Lin Su, Jyh-Chin Yang, Haur Lee, Fuu Sheu, Chun-Hua Hsu, Shuei-Liong Lin and Lu-Ping Chow J Immunol 2015; 194:3997-4007; Prepublished online 13 March 2015; doi: 10.4049/jimmunol.1401852 Downloaded from http://www.jimmunol.org/content/194/8/3997 References This article cites 66 articles, 25 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/194/8/3997.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 26, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology The C-Terminal Disulfide Bonds of Helicobacter pylori GroES Are Critical for IL-8 Secretion via the TLR4-Dependent Pathway in Gastric Epithelial Cells Yu-Lin Su,* Jyh-Chin Yang,† Haur Lee,* Fuu Sheu,‡ Chun-Hua Hsu,x Shuei-Liong Lin,{ and Lu-Ping Chow* Helicobacter pylori GroES (HpGroES), a potent immunogen, is a secreted virulence factor that stimulates production of proin- flammatory cytokines and may contribute to gastric carcinogenesis. HpGroES is larger than other bacterial orthologs because of an additional C-terminal region, known as domain B. We found that the HpGroES-induced IL-8 release by human gastric epithelial cells was dependent on activation of the MAPK and NF-kB pathways. HpGroES lacking domain B was unable to induce IL-8 release. Additionally, a TLR4 inhibitor significantly inhibited IL-8 secretion and reduced HpGroES-induced activa- Downloaded from tion of MAPKs. Furthermore, HpGroES-induced IL-8 release by primary gastric epithelial cells from TLR42/2 mice was significantly lower than from wild-type mice. We also found that HpGroES bound to TLR4 in cell lysates and colocalized with TLR4 on the cell membrane only when domain B was present. We then constructed two deletion mutants lacking C-terminal regions and mutants with point mutations of two of the four cysteine residues, C111 and C112, in domain B and found that the deletion mutants and a double mutant lacking the C94–C111 and C95–C112 disulfide bonds were unable to interact with TLR4 or induce IL-8 release. We conclude that HpGroES, in which a unique conformational structure, domain B, is generated by these two http://www.jimmunol.org/ disulfide bonds, induces IL-8 secretion via a TLR4-dependent mechanism. The Journal of Immunology, 2015, 194: 3997–4007. elicobacter pylori is a Gram-negative, microaerophilic epithelial and immune cells (9–11). It is well recognized that re- bacterium that selectively colonizes the human stomach lease of these proinflammatory cytokines is closely linked to the H (1). H. pylori infection is a major cause of chronic pathogenesis of H. pylori–associated gastric cancer (12, 13). In- gastritis and peptic ulcer disease and is highly related to gastric duction of cytokine secretion by H. pylori depends on both the adenocarcinoma and MALT lymphoma (2). Despite a recent de- host genetic background and microbial virulence (9). Among cline in infection rates, the prevalence rate of H. pylori remains at these cytokines, IL-8 is the most highly expressed gene in nearly 50% of the world’s population, and the associated gastric H. pylori–infected gastric epithelial cells and appears to play a major by guest on September 26, 2021 cancer is the second leading cause of cancer-related death role in the epithelial cell response to H. pylori infection and in the worldwide. The most remarkable feature of persistent H. pylori pathological processes leading to gastric disease (14, 15). Several infection is that it causes inflammatory responses, which is an studies have demonstrated increased IL-8 production and secre- important risk factor for malignancy (3). H. pylori infection tion in response to H. pylori both in vivo and in vitro (16, 17). induces gastritis with infiltration of neutrophils, macrophages, Gastric mucosal IL-8 levels show a positive correlation with the dendritic cells, as well as T and B lymphocytes into the gastric degree of stomach corpus inflammation, and IL-8 expression is mucosa (4–8) in addition to the accumulation of various cyto- also highly increased in gastric cancer (18, 19). IL-8 production kines, including TNF-a, IL-1b, IL-6, and IL-8 secreted by gastric by gastric epithelial cells is enhanced by the virulence factor cytotoxin-associated gene (cag) pathogenicity island and other factors from H. pylori (20–23). We have previously reported that *Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, † H. pylori Hp National Taiwan University, Taipei 100, Taiwan; Department of Internal Medicine, GroES ( GroES) can induce the production and se- Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan; cretion of proinflammatory cytokines, including IL-8, IL-6, IL-1b, ‡ x Department of Horticulture, National Taiwan University, Taipei 106, Taiwan; De- and TNF-a, by human PBMCs and trigger IL-8 production and partment of Agricultural Chemistry, National Taiwan University, Taipei 106, Taiwan; and {Graduate Institute of Physiology, College of Medicine, National Taiwan Uni- secretion by gastric epithelial cells (24). versity, Taipei 100, Taiwan HpGroES, also referred to as heat shock protein (HSP) A, is an Received for publication July 21, 2014. Accepted for publication February 9, 2015. unusual homolog of the essential bacterial GroES chaperonin This work was supported by National Science Council Grant NSC 101-2325-B-002- family (25), the members of which serve as cochaperonins of 065, the Liver Disease Prevention and Treatment Research Foundation, and the the heptameric GroEL/GroES barrel complex, which mediates the Ministry of Education, Taiwan. refolding of a variety of nonnative proteins (26). In addition to Address correspondence and reprint requests to Prof. Lu-Ping Chow, Graduate Insti- tute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan the highly conserved GroES chaperonin domain, named domain University, No. 1, Jen-Ai Road, Taipei 100, Taiwan. E-mail address: chowip@ntu. A, HpGroES contains a C-terminal extension domain named do- edu.tw main B (residues 91–118), which is absent in the other GroES Abbreviations used in this article: Cag, cytotoxin-associated gene; CD, circular di- members (25). Domain B consists of 28 aa, including 8 histi- chroism; 4CR, four-cysteine ring; EcGroES, Escherichia coli GroES; HA, hemag- glutinin; HpGroES, Helicobacter pylori GroES; HSP, heat shock protein; KC, dine and 4 cysteine residues, with the latter forming two disul- keratinocyte-derived chemokine; OxPAPC, oxidized 1-palmitoyl-2-arachidonoyl-sn- fide bonds, C94–C111 and C95–C112, generating a closed-loop glycero-3-phosphocholine; PGN, peptidoglycan; WT, wild-type. structure (27). Apart from its cochaperone activity, HpGroES Copyright Ó 2015 by The American Association of Immunologists, Inc. 0022-1767/15/$25.00 plays important roles in nickel homeostasis and urease activation www.jimmunol.org/cgi/doi/10.4049/jimmunol.1401852 3998 C TERMINI CYSTEINES NEEDED FOR HpGroES-INDUCED IL-8 VIA TLR4 (25, 28, 29). Besides these roles in intracellular locations (30), DMEM. All cells were grown at 37˚C with 5% CO2 in medium supple- HpGroES is able to gain access to the extracellular compartment mented with 10% FBS and 100 U/ml penicillin-streptomycin, whereas and is highly antigenic (29, 31) and is specifically recognized by HEK293/TLR4-HA cultures were also supplemented with 100 mg/ml blasticidin. serum Abs in H. pylori–infected patients and is considered a potential candidate for vaccine development and diagnosis of Immunofluorescence staining H. pylori infection (32, 33). KATO-III and HEK293/TLR4-HA cells were seeded on coverslips over- The increased production and secretion of proinflammatory night, then treated for 1 h with 0.05 mM HpGroES or domain A at 4˚C, then cytokines induced by HpGroES has been shown to contribute to fixed with 4% paraformaldehyde in PBS for 15 min at room temperature, gastric inflammation (7, 16, 34). However, the molecular mecha- blocked by incubation for 1 h at room temperature with 5% BSA, and immunostained with rabbit Abs against HpGroES (1:200) or mouse mAb nism of proinflammatory cytokine induction has not been eluci- against TLR4 (1:200) followed by FITC- or tetramethylrhodamine iso- dated. In this study, we found that HpGroES induced IL-8 thiocyanate–labeled secondary Abs (1:500) and staining of nuclei with secretion by gastric carcinoma cells by activating the MAPK and DAPI (1:1000), and then images were captured using a TCS SP5 confocal NF-kB pathways via a TLR4-dependent mechanism. In TLR4- microscope (Leica, Wetzlar, Germany). deficient mice, HpGroES failed to induce production of the Expression and purification of HpGroES, domain A, and mouse IL-8 homolog keratinocyte-derived chemokine (KC). We Escherichia coli GroES also demonstrated direct binding of HpGroES, but not domain A Hp E. coli Ec alone, to TLR4 on gastric epithelial cells and TLR4-overexpressing The genes encoding GroES, domain A, and GroES ( GroES) were cloned using the expression vector pQE30 as described previously cells.
Load more

Recommended publications
  • RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
    RT² Profiler PCR Array (96-Well Format and 384-Well [4 x 96] Format) Human Toll-Like Receptor Signaling Pathway Cat. no. 330231 PAHS-018ZA For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 5700, 7000, 7300, 7500, Format A 7700, 7900HT, ViiA™ 7 (96-well block); Bio-Rad® models iCycler®, iQ™5, MyiQ™, MyiQ2; Bio-Rad/MJ Research Chromo4™; Eppendorf® Mastercycler® ep realplex models 2, 2s, 4, 4s; Stratagene® models Mx3005P®, Mx3000P®; Takara TP-800 RT² Profiler PCR Array, Applied Biosystems models 7500 (Fast block), 7900HT (Fast Format C block), StepOnePlus™, ViiA 7 (Fast block) RT² Profiler PCR Array, Bio-Rad CFX96™; Bio-Rad/MJ Research models DNA Format D Engine Opticon®, DNA Engine Opticon 2; Stratagene Mx4000® RT² Profiler PCR Array, Applied Biosystems models 7900HT (384-well block), ViiA 7 Format E (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (96-well block) Format F RT² Profiler PCR Array, Roche LightCycler 480 (384-well block) Format G RT² Profiler PCR Array, Fluidigm® BioMark™ Format H Sample & Assay Technologies Description The Human Toll-Like Receptor (TLR) Signaling Pathway RT² Profiler PCR Array profiles the expression of 84 genes central to TLR-mediated signal transduction and innate immunity. The TLR family of pattern recognition receptors (PRRs) detects a wide range of bacteria, viruses, fungi and parasites via pathogen-associated molecular patterns (PAMPs). Each receptor binds to specific ligands, initiates a tailored innate immune response to the specific class of pathogen, and activates the adaptive immune response.
    [Show full text]
  • An Immunologist's Perspective on Nutrition, Immunity, and Infectious
    © 2009 Poultry Science Association, Inc. An immunologist’s perspective on nutrition, immunity, and infectious diseases: 1 Introduction and overview M. H. Kogut *2 and K. Klasing † * Southern Plains Agricultural Research Center, USDA-ARS, College Station, TX 77845; and † Department of Avian Sciences, University of California, Davis 95616 Primary Audience: Poultry Nutritionists, Immunologists, Veterinarians, Researchers SUMMARY The immune system is a multifaceted arrangement of membranes (skin, epithelial, and mucus), cells, and molecules whose function is to eradicate invading pathogens or cancer cells from a host. Working together, the various components of the immune system perform a balancing act of being lethal enough to kill pathogens or cancer cells yet specific so as not to cause extensive damage to “self” tissues of the host. A functional immune system is a requirement of a healthy life in modern animal production. Yet infectious diseases still represent a serious drain on the economics (reduced production, cost of therapeutics, and vaccines) and welfare of animal agriculture. The interaction involving nutrition and immunity and how the host deals with infectious agents is a strategic deter- minant in animal health. Almost all nutrients in the diet play a fundamental role in sustaining an op- timal immune response, such that deficient and excessive intakes can have negative consequences on immune status and susceptibility to a variety of pathogens. Dietary components can regulate physiological functions of the body; interacting with the immune response is one of the most im- portant functions of nutrients. The pertinent question to be asked and answered in the current era of poultry production is whether the level of nutrients that maximizes production in commercial diets is sufficient to maintain competence of immune status and disease resistance.
    [Show full text]
  • Activation of Toll-Like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth
    Published OnlineFirst March 22, 2011; DOI: 10.1158/0008-5472.CAN-10-1993 Cancer Microenvironment and Immunology Research Activation of Toll-like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth Zhenyu Cai, Amir Sanchez, Zhongcheng Shi, Tingting Zhang, Mingyao Liu, and Dekai Zhang Abstract Increasing evidence showed that Toll-like receptors (TLR), key receptors in innate immunity, play a role in cancer progression and development but activation of different TLRs might exhibit the exact opposite outcome, antitumor or protumor effects. TLR function has been extensively studied in innate immune cells, so we investigated the role of TLR signaling in breast cancer epithelial cells. We found that TLR5 was highly expressed in breast carcinomas and that TLR5 signaling pathway is overly responsive in breast cancer cells. Interestingly, flagellin/TLR5 signaling in breast cancer cells inhibits cell proliferation and an anchorage-independent growth, a hallmark of tumorigenic transformation. In addition, the secretion of soluble factors induced by flagellin contributed to the growth-inhibitory activity in an autocrine fashion. The inhibitory activity was further confirmed in mouse xenografts of human breast cancer cells. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy. Cancer Res; 71(7); 1–10. Ó2011 AACR. Introduction (16, 17). Thus, the function and biological importance of TLRs expressed on various tumor cells seem complex. Toll-like receptors (TLR) are membrane-bound receptors Unlike other TLR family members, TLR5 is not expressed on that play key roles in both the innate and adaptive immune mouse macrophages and conventional dendritic cells (DC).
    [Show full text]
  • Bacterial Flagellin—A Potent Immunomodulatory Agent
    OPEN Experimental & Molecular Medicine (2017) 49, e373; doi:10.1038/emm.2017.172 Official journal of the Korean Society for Biochemistry and Molecular Biology www.nature.com/emm REVIEW Bacterial flagellin—a potent immunomodulatory agent Irshad A Hajam1, Pervaiz A Dar2, Imam Shahnawaz2, Juan Carlos Jaume2 and John Hwa Lee1 Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that contributes to the adhesion and invasion of host cells, but now it has emerged as a potent immune activator, shaping both the innate and adaptive arms of immunity during microbial infections. In this review, we summarize our understanding of bacterial flagellin and host immune system interactions and the role flagellin as an adjuvant, anti-tumor and radioprotective agent, and we address important areas of future research interests. Experimental & Molecular Medicine (2017) 49, e373; doi:10.1038/emm.2017.172; published online 1 September 2017 INTRODUCTION vaccines. Even though all the adjuvants studied so far have The immune system has evolved to fight off microbial invasion proven to be effective, flagellin, a TLR5 agonist, has been through the coordinated action of the innate and adaptive arms shown more promising results without any major side effects. of the immunity. Innate immune cells respond to a variety of Flagellin is the structural component of the flagellum, a stimuli, including bacterial, viral, parasitic or fungal infections, locomotory organ that is mostly associated with Gram-negative via members of structurally related receptors termed toll-like bacteria. It is characterized by highly conserved N- and receptors (TLRs).
    [Show full text]
  • Receptor 5/Toll-Like Receptor 4 Complexes Involves Signaling Via
    Induction of Macrophage Nitric Oxide Production by Gram-Negative Flagellin Involves Signaling Via Heteromeric Toll-Like Receptor 5/Toll-Like Receptor 4 Complexes This information is current as of September 25, 2021. Steven B. Mizel, Anna N. Honko, Marlena A. Moors, Pameeka S. Smith and A. Phillip West J Immunol 2003; 170:6217-6223; ; doi: 10.4049/jimmunol.170.12.6217 http://www.jimmunol.org/content/170/12/6217 Downloaded from References This article cites 50 articles, 26 of which you can access for free at: http://www.jimmunol.org/content/170/12/6217.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Induction of Macrophage Nitric Oxide Production by Gram-Negative Flagellin Involves Signaling Via Heteromeric Toll-Like Receptor 5/Toll-Like Receptor 4 Complexes1 Steven B.
    [Show full text]
  • Recognition of Lipopolysaccharide Pattern by TLR4 Complexes
    OPEN Experimental & Molecular Medicine (2013) 45, e66; doi:10.1038/emm.2013.97 & 2013 KSBMB. All rights reserved 2092-6413/13 www.nature.com/emm REVIEW Recognition of lipopolysaccharide pattern by TLR4 complexes Beom Seok Park1 and Jie-Oh Lee2 Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. Minute amounts of LPS released from infecting pathogens can initiate potent innate immune responses that prime the immune system against further infection. However, when the LPS response is not properly controlled it can lead to fatal septic shock syndrome. The common structural pattern of LPS in diverse bacterial species is recognized by a cascade of LPS receptors and accessory proteins, LPS binding protein (LBP), CD14 and the Toll-like receptor4 (TLR4)–MD-2 complex. The structures of these proteins account for how our immune system differentiates LPS molecules from structurally similar host molecules. They also provide insights useful for discovery of anti-sepsis drugs. In this review, we summarize these structures and describe the structural basis of LPS recognition by LPS receptors and accessory proteins. Experimental & Molecular Medicine (2013) 45, e66; doi:10.1038/emm.2013.97; published online 6 December 2013 Keywords: lipopolysaccharide (LPS); Toll-like receptor 4 (TLR4); MD-2; CD14; LBP INTRODUCTION the cell surface by a glycosylphosphatidylinositol anchor. CD14 In the initial phase of infection, the innate immune system splits LPS aggregates into monomeric molecules and presents generates a rapid inflammatory response that blocks the them to the TLR4–MD-2 complex. Aggregation of the TLR4– growth and dissemination of the infectious agent.
    [Show full text]
  • Expression and Function in Aging Cutting Edge
    Cutting Edge: Impaired Toll-Like Receptor Expression and Function in Aging Mary Renshaw, Julie Rockwell, Carrie Engleman, Andrew Gewirtz, Jacqueline Katz and Suryaprakash Sambhara This information is current as of October 1, 2021. J Immunol 2002; 169:4697-4701; ; doi: 10.4049/jimmunol.169.9.4697 http://www.jimmunol.org/content/169/9/4697 Downloaded from References This article cites 27 articles, 5 of which you can access for free at: http://www.jimmunol.org/content/169/9/4697.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 1, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology ● Cutting Edge: Impaired Toll-Like Receptor Expression and Function in Aging Mary Renshaw,* Julie Rockwell,* Carrie Engleman,* Andrew Gewirtz,† Jacqueline Katz,* and Suryaprakash Sambhara1* illness in frail elderly individuals (4). The reduced efficacy of in- Toll-like receptors (TLR) are pattern recognition receptors fluenza vaccines in the elderly is likely, at least in part, due to that recognize conserved molecular patterns on microbes and reduced immune responses to vaccination.
    [Show full text]
  • Relevance of Single-Nucleotide Polymorphisms in Human TLR Genes to Infectious and Inflammatory Diseases and Cancer
    Genes and Immunity (2014) 15, 199–209 & 2014 Macmillan Publishers Limited All rights reserved 1466-4879/14 www.nature.com/gene REVIEW Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer A Trejo-de la O1,3, P Herna´ndez-Sance´n2,3 and C Maldonado-Bernal1 Innate and adaptive immune responses in humans have evolved as protective mechanisms against infectious microorganisms. Toll-like receptors (TLRs) have an important role in the recognition of invading microorganisms. TLRs are the first receptors to detect potential pathogens and to initiate the immune response, and they form the crucial link between the innate and adaptive immune responses. TLRs also have an important role in the pathophysiology of infectious and inflammatory diseases. Increasing data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single-nucleotide polymorphisms (SNPs) within TLR genes, resulting in an altered susceptibility to infectious or inflammatory disease that might contribute to the pathogenesis of complex diseases such as cancer. The associations between diseases and SNPs are in the early stage of discovery. Important clinical insights are emerging, and these polymorphisms provide new understanding of common diseases. This review summarizes and discusses the studies that shed light on the relevance of these polymorphisms in human infectious and inflammatory diseases and cancer. Genes and Immunity (2014) 15, 199–209; doi:10.1038/gene.2014.10; published online 13 March 2014 INTRODUCTION complex1,9 and is also involved in the signaling response to other The family of Toll-like receptors (TLRs) has been identified as key exogenous stimuli.
    [Show full text]
  • TLR5 Participates in the TLR4 Receptor Complex and Biases Towards Myd88-Dependent
    bioRxiv preprint doi: https://doi.org/10.1101/792705; this version posted October 3, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. 1 TLR5 participates in the TLR4 receptor complex and biases towards MyD88-dependent 2 signaling in environmental lung injury 3 Salik Hussain1*, Collin G Johnson1*, Joseph Sciurba1*, Xianglin Meng1, Vandy P Stober1, Caini 4 Liu2, Jaime M Cyphert-Daly1, Katarzyna Bulek2,3, Wen Qian2, Alma Solis1, Yosuke Sakamachi1, 5 Carol S Trempus1, Jim J Aloor4, Kym M Gowdy 4, W. Michael Foster5, John W Hollingsworth5, 6 Robert M Tighe5, Xiaoxia Li2, Michael B Fessler1, Stavros Garantziotis1# 7 1 National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA 8 2 Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA 9 3 Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, 10 Jagiellonian University, Krakow, Poland 11 4 East Carolina University Brody School of Medicine, Greenville, NC 27834, USA 12 5 Duke University Medical Center, Durham, NC 27710, USA 13 *equal contribution as first authors 14 # Corresponding Author and Lead Contact 15 Current Affiliations: CG Johnson : Baylor University. J Sciurba : NC State University. JM 16 Cyphert-Daly : Duke University. JJ Aloor : East Carolina University 17 18 Running title: 19 Tlr5 participates in Tlr4 signaling 20 Conflict of Interest statement: 21 The authors have declared that no conflict of interest exists.
    [Show full text]
  • Cellular and Molecular Regulation of Innate Inflammatory Responses
    Cellular & Molecular Immunology (2016) 13, 711–721 & 2016 CSI and USTC All rights reserved 2042-0226/16 $32.00 www.nature.com/cmi REVIEW Cellular and molecular regulation of innate inflammatory responses Juan Liu1 and Xuetao Cao1,2 Innate sensing of pathogens by pattern-recognition receptors (PRRs) plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non- immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and regulation of innate immunity and inflammatory responses. Cellular & Molecular Immunology (2016) 13, 711–721; doi:10.1038/cmi.2016.58; published online 31 October 2016 Keywords: dendritic cells; inflammation; innate lymphoid cells; innate signaling; pattern-recognition receptors (PRRs) INTRODUCTION pathway or the MyD88-independent but TRIF-dependent Innate immune system constitutes the first critical line against pathway, subsequently leading to activation of mitogen-
    [Show full text]
  • The Immune System
    CAMPBELL BIOLOGY IN FOCUS URRY • CAIN • WASSERMAN • MINORSKY • REECE 35 The Immune System Lecture Presentations by Kathleen Fitzpatrick and Nicole Tunbridge, Simon Fraser University © 2016 Pearson Education, Inc. SECOND EDITION Overview: Recognition and Response . Pathogens, agents that cause disease, infect a wide range of animals, including humans . The immune system enables an animal to avoid or limit many infections . All animals have innate immunity, a defense that is active immediately upon infection . Vertebrates also have adaptive immunity © 2016 Pearson Education, Inc. Figure 35.1 © 2016 Pearson Education, Inc. Innate immunity includes barrier defenses . A small set of receptor proteins bind molecules or structures common to viruses, bacteria, or other microbes . Binding an innate immune receptor activates internal defensive responses to a broad range of pathogens © 2016 Pearson Education, Inc. Adaptive immunity, or acquired immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances . It involves a very specific response to pathogens © 2016 Pearson Education, Inc. Figure 35.2 Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY Barrier defenses: (all animals) Skin • Recognition of traits shared Mucous membranes by broad ranges of Secretions pathogens, using a small set of receptors Internal defenses: Phagocytic cells • Rapid response Natural killer cells Antimicrobial proteins Inflammatory response ADAPTIVE IMMUNITY Humoral response: (vertebrates only) Antibodies defend against • Recognition of traits infection in body fluids. specific to particular pathogens, using a vast Cell-mediated response: array of receptors Cytotoxic cells defend against infection in body cells. • Slower response © 2016 Pearson Education, Inc. Concept 35.1: In innate immunity, recognition and response rely on traits common to groups of pathogens .
    [Show full text]
  • Immunity and Systemic Activation of TLR5-Dependent Neutralization
    Deletion of Flagellin's Hypervariable Region Abrogates Antibody-Mediated Neutralization and Systemic Activation of TLR5-Dependent Immunity This information is current as of September 27, 2021. Clément Nempont, Delphine Cayet, Martin Rumbo, Coralie Bompard, Vincent Villeret and Jean-Claude Sirard J Immunol 2008; 181:2036-2043; ; doi: 10.4049/jimmunol.181.3.2036 http://www.jimmunol.org/content/181/3/2036 Downloaded from References This article cites 40 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/181/3/2036.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Deletion of Flagellin’s Hypervariable Region Abrogates Antibody-Mediated Neutralization and Systemic Activation of TLR5-Dependent Immunity1 Cle´ment Nempont,* Delphine Cayet,* Martin Rumbo,† Coralie Bompard,‡ Vincent Villeret,‡ and Jean-Claude Sirard2* TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs).
    [Show full text]