RRC ID 48851
著者 Uchiyama R, Yonehara S, Taniguchi S, Ishido S, Ishii KJ, Tsutsui H.
タイトル Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo.
ジャーナル J Immunol
Abstract CD4+ Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4+ Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard-/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas-/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas-/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo.
巻・号 199(3)
ページ 1122-1130
公開日 2017-8-1
DOI 10.4049/jimmunol.1601373
PII jimmunol.1601373
PMID 28674179
MeSH Animals Apoptosis Regulatory Proteins / deficiency Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism CARD Signaling Adaptor Proteins Cell Differentiation Inflammasomes / immunology* Interleukin-1beta / administration & dosage Interleukin-1beta / immunology* Listeria monocytogenes / immunology* Listeria monocytogenes / pathogenicity Listeriosis / immunology* Mice Mice, Inbred C57BL Mice, Knockout Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism Receptors, Interleukin-1 Type I / genetics Receptors, Interleukin-1 Type I / immunology Spleen / immunology T-Box Domain Proteins / genetics T-Box Domain Proteins / metabolism Th1 Cells / immunology* Th17 Cells / immunology* fas Receptor / deficiency fas Receptor / genetics fas Receptor / metabolism*
IF 4.886
引用数 11
リソース情報
実験動物マウス RBRC00144