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Gang Peng - One of the best experts on this subject based on the ideXlab platform.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:: The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN-ɣ and IL-13. Here we investigated the transcriptome of CD8ɣ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8ɣ13 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function. METHODS: In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS: To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS: The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:BACKGROUND The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as "unrestricted" or "atypical"). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. METHODS In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8ɣ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN- and IL-13. Here we investigated the transcriptome of CD813 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD813 polarization included IL-5 in addition to IFN-gamma and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD813 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD813 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function.
Raymond M Johnson - One of the best experts on this subject based on the ideXlab platform.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:: The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN-ɣ and IL-13. Here we investigated the transcriptome of CD8ɣ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8ɣ13 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function. METHODS: In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS: To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS: The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:BACKGROUND The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as "unrestricted" or "atypical"). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. METHODS In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8ɣ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN- and IL-13. Here we investigated the transcriptome of CD813 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD813 polarization included IL-5 in addition to IFN-gamma and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD813 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD813 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function.
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an atypical cd8 t cell response to chlamydia muridarum genital tract infections includes t cells that produce interleukin 13
Immunology, 2014Co-Authors: Raymond M Johnson, Micah S Kerr, James E SlavenAbstract:Chlamydia trachomatis urogenital serovars D-K are intracellular bacterial pathogens that replicate almost exclusively in human reproductive tract epithelium. In the C. muridarum mouse model for human Chlamydia genital tract infections CD4 T helper type 1 cell responses mediate protective immunity while CD8 T-cell responses have been associated with scarring and infertility. Scarring mediated by CD8 T cells requires production of tumour necrosis factor-α (TNF-α); however, TNF-α is associated with protective immunity mediated by CD4 T cells. The latter result suggests that TNF-α in-and-of itself may not be the sole determining factor in Immunopathology. CD8 T cells mediating Immunopathology presumably do something in addition to producing TNF-α that is detrimental during resolution of genital tract infections. To investigate the mechanism underlying CD8 Immunopathology we attempted to isolate Chlamydia-specific CD8 T-cell clones from mice that self-cleared genital tract infections. They could not be derived with antigen-pulsed irradiated naive splenocytes; instead derivation required use of irradiated immune splenocyte antigen-presenting cells. The Chlamydia-specific CD8 T-cell clones had relatively low cell surface CD8 levels and the majority were not restricted by MHC class Ia molecules. They did not express Plac8, and had varying abilities to terminate Chlamydia replication in epithelial cells. Two of the five CD8 clones produced interleukin-13 (IL-13) in addition to IL-2, TNF-α, IL-10 and interferon-γ. IL-13-producing Chlamydia-specific CD8 T cells may contribute to Immunopathology during C. muridarum genital tract infections based on known roles of TNF-α and IL-13 in scar formation.
Markus M Heimesaat - One of the best experts on this subject based on the ideXlab platform.
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Campylobacter jejuni Induces Acute Enterocolitis in Gnotobiotic IL-102/2Mice via Toll-Like-Receptor-2 and-4 Signaling
2016Co-Authors: Leamaxie Haag, Stefan Bereswill, Bettina Otto, Rita Plickert, Andre ́ Fischer, Anja A. Kühl, Ulf B. Göbel, Markus M HeimesaatAbstract:Background: Campylobacter jejuni is a leading cause of foodborne bacterial enterocolitis worldwide. Investigation of Immunopathology is hampered by a lack of suitable vertebrate models. We have recently shown that gnotobiotic mice as well as conventional IL-102/2 animals are susceptible to C. jejuni infection and develop intestinal immune responses. However, clinical symptoms of C. jejuni infection were rather subtle and did not reflect acute bloody diarrhea seen in human campylobacteriosis. Methodology/Principal Findings: In order to overcome these limitations we generated gnotobiotic IL-102/2 mice by quintuple antibiotic treatment starting right after weaning. The early treatment was essential to prevent these animals from chronic colitis. Following oral infection C. jejuni colonized the gastrointestinal tract at high levels and induced acute enterocolitis within 7 days as indicated by bloody diarrhea and pronounced histopathological changes of the colonic mucosa. Immunopathology was further characterized by increased numbers of apoptotic cells, regulatory T-cells, T- and B-lymphocytes as well as elevated TNF-a, IFN-c, and MCP-1 concentrations in the inflamed colon. The induction of enterocolitis was specific for C. jejuni given that control animals infected with a commensal E. coli strain did not display any signs of disease. Most strikingly, intestinal Immunopathology was ameliorated in mice lacking Toll-like-receptors-2 or-4 indicating that C. jejuni lipoproteins and lipooligosaccharide are essential for induction and progression o
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campylobacter jejuni induces acute enterocolitis in gnotobiotic il 10 mice via toll like receptor 2 and 4 signaling
PLOS ONE, 2012Co-Authors: Leamaxie Haag, Andre Fischer, Stefan Bereswill, Bettina Otto, Rita Plickert, Anja A Kuhl, Ulf B Gobel, Markus M HeimesaatAbstract:Background Campylobacter jejuni is a leading cause of foodborne bacterial enterocolitis worldwide. Investigation of Immunopathology is hampered by a lack of suitable vertebrate models. We have recently shown that gnotobiotic mice as well as conventional IL-10(-/-) animals are susceptible to C. jejuni infection and develop intestinal immune responses. However, clinical symptoms of C. jejuni infection were rather subtle and did not reflect acute bloody diarrhea seen in human campylobacteriosis. Methodology/principal findings In order to overcome these limitations we generated gnotobiotic IL-10(-/-) mice by quintuple antibiotic treatment starting right after weaning. The early treatment was essential to prevent these animals from chronic colitis. Following oral infection C. jejuni colonized the gastrointestinal tract at high levels and induced acute enterocolitis within 7 days as indicated by bloody diarrhea and pronounced histopathological changes of the colonic mucosa. Immunopathology was further characterized by increased numbers of apoptotic cells, regulatory T-cells, T- and B-lymphocytes as well as elevated TNF-α, IFN-γ, and MCP-1 concentrations in the inflamed colon. The induction of enterocolitis was specific for C. jejuni given that control animals infected with a commensal E. coli strain did not display any signs of disease. Most strikingly, intestinal Immunopathology was ameliorated in mice lacking Toll-like-receptors-2 or -4 indicating that C. jejuni lipoproteins and lipooligosaccharide are essential for induction and progression of Immunopathology. Conclusion/significance Gnotobiotic IL-10(-/-) mice develop acute enterocolitis following C. jejuni infection mimicking severe episodes of human campylobacteriosis and are thus well suited to further dissect mechanisms underlying Campylobacter infections in vivo.
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gram negative bacteria aggravate murine small intestinal th1 type Immunopathology following oral infection with toxoplasma gondii
Journal of Immunology, 2006Co-Authors: Markus M Heimesaat, Daniela Struck, Andre Fischer, Stefan Bereswill, David Fuchs, Julia Niebergall, Hannahkatharina Jahn, Ildiko R Dunay, Annette Moter, Dorothee Maria GescherAbstract:Oral infection of susceptible mice with Toxoplasma gondii results in Th1-type Immunopathology in the ileum. We investigated gut flora changes during ileitis and determined contributions of gut bacteria to intestinal inflammation. Analysis of the intestinal microflora revealed that ileitis was accompanied by increasing bacterial load, decreasing species diversity, and bacterial translocation. Gram-negative bacteria identified as Escherichia coli and Bacteroides/Prevotella spp. accumulated in inflamed ileum at high concentrations. Prophylactic or therapeutic administration of ciprofloxacin and/or metronidazole ameliorated ileal Immunopathology and reduced intestinal NO and IFN-gamma levels. Most strikingly, gnotobiotic mice in which cultivable gut bacteria were removed by quintuple antibiotic treatment did not develop ileitis after Toxoplasma gondii infection. A reduction in total numbers of lymphocytes was observed in the lamina propria of specific pathogen-free (SPF), but not gnotobiotic, mice upon development of ileitis. Relative numbers of CD4(+) T cells did not differ in naive vs infected gnotobiotic or SPF mice, but infected SPF mice showed a significant increase in the frequencies of activated CD4(+) T cells compared with gnotobiotic mice. Furthermore, recolonization with total gut flora, E. coli, or Bacteroides/Prevotella spp., but not Lactobacillus johnsonii, induced Immunopathology in gnotobiotic mice. Animals recolonized with E. coli and/or total gut flora, but not L. johnsonii, showed elevated ileal NO and/or IFN-gamma levels. In conclusion, Gram-negative bacteria, i.e., E. coli, aggravate pathogen-induced intestinal Th1-type Immunopathology. Thus, pathogen-induced acute ileitis may prove useful to study bacteria-host interactions in small intestinal inflammation and to test novel therapies based on modulation of gut flora.
Norma Olivaresstrank - One of the best experts on this subject based on the ideXlab platform.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:: The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN-ɣ and IL-13. Here we investigated the transcriptome of CD8ɣ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8ɣ13 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function. METHODS: In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS: To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS: The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8γ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:BACKGROUND The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as "unrestricted" or "atypical"). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. METHODS In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. RESULTS To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia Immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. CONCLUSIONS The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.
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a class ii restricted cd8ɣ13 t cell clone protects during chlamydia muridarum genital tract infection
The Journal of Infectious Diseases, 2020Co-Authors: Raymond M Johnson, Norma Olivaresstrank, Gang PengAbstract:The T cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I-restricted, referred to as "unrestricted" or "atypical". We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included IFN- and IL-13. Here we investigated the transcriptome of CD813 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD813 polarization included IL-5 in addition to IFN-gamma and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD813 T cell clone to determine whether either influenced bacterial clearance or Immunopathology during Chlamydia muridarum genital tract infections. To our surprise, an adoptively transferred CD813 T cell clone was remarkably proficient at preventing chlamydia Immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly alter Immunopathology. Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T cell clones are MHC class II-restricted. MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation, or diminish CD4 T cell numbers or impair their function.
Stephen C Bunnell - One of the best experts on this subject based on the ideXlab platform.
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cd209a synergizes with dectin 2 and mincle to drive severe th17 cell mediated schistosome egg induced Immunopathology
Cell Reports, 2018Co-Authors: Parisa Kalantari, Yoelkys Morales, Emily A Miller, Luis D Jaramillo, Holly Ponichtera, Marcel Wuethrich, Cheolho Cheong, Maria C Seminario, Joanne M Russo, Stephen C BunnellAbstract:The Immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe Immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated Immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs.
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CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology
Elsevier, 2018Co-Authors: Parisa Kalantari, Yoelkys Morales, Emily A Miller, Luis D Jaramillo, Holly Ponichtera, Marcel Wuethrich, Cheolho Cheong, Maria C Seminario, Joanne M Russo, Stephen C BunnellAbstract:Summary: The Immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe Immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated Immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs. : Kalantari et al. demonstrate the role of CD209a (SIGNR5) in the development of Th17 cell-mediated Immunopathology in murine schistosomiasis. CD209a drives proinflammatory cytokine production in synergy with Dectin-2 and Mincle, each acting via distinct signaling pathways. These findings denote C-type lectin receptor cross talk resulting in severe helminthic disease. Keywords: Schistosoma mansoni, Immunopathology, dendritic cells, Th17 cells, CD209a, Dectin-2, Mincle, Syk, Raf-1, IL-1
