Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo

Area of Science:

• Immunology
• Cellular Biology
• Microbiology

Background:

• CD4+ T helper (Th) cells differentiate into effector subsets crucial for immune responses.
• IFN-γ and IL-17 double-producing Th17/Th1 cells are implicated in autoimmune diseases and infections.
• The precise induction mechanisms of Th17/Th1 cells during pathogen infection remain unclear.

Purpose of the Study:

• To elucidate the molecular mechanisms of Th17/Th1 cell induction during bacterial infection.
• To investigate the roles of inflammasome, Fas, and IL-1β in Th17/Th1 cell differentiation.

Main Methods:

• Infection of wild-type and knockout mice (Pycard-/-, Fas-/-) with Listeria monocytogenes.
• Analysis of Th17/Th1 cell induction, T-bet and Rorγt expression in spleens.
• Assessment of IL-1β production, IL-1 receptor 1 (IL-1R1) involvement, and recombinant IL-1β supplementation.

Main Results:

• Th17/Th1 cells were induced in wild-type mice infected with Listeria monocytogenes.
• Inflammasome (Pycard-/-) and Fas (Fas-/-) deficiencies abolished Th17/Th1 induction.
• IL-1β, produced via inflammasome and Fas pathways, acts on IL-1R1 on T cells to induce Th17/Th1 cells, rescuing mortality in Fas-/- mice.

Conclusions:

• Cooperative mechanisms involving inflammasome and Fas-dependent IL-1β production are essential for Th17/Th1 induction during bacterial infection.
• IL-1β signaling through IL-1R1 on T cells is critical for Th17/Th1 cell differentiation.
• This study enhances understanding of Th17/Th1 cell induction during pathogenic microbial infections.