| First Author | Uchiyama R | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 3 | Pages | 1122-1130 |
| PubMed ID | 28674179 | Mgi Jnum | J:250824 |
| Mgi Id | MGI:6099473 | Doi | 10.4049/jimmunol.1601373 |
| Citation | Uchiyama R, et al. (2017) Inflammasome and Fas-Mediated IL-1beta Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo. J Immunol 199(3):1122-1130 |
| abstractText | 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-gamma 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-1beta 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 Rorgammat. 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-1beta production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas(-/-) mice, whereas supplementation with recombinant IL-1beta 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-1beta stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1beta, 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. |
