Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

eLife

Isabella Rauch¹  Katherine A Deets²  Randilea Nichols Doyle²  Russell E Vance³ 

[1] Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States;Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States;

关键词: inflammasome;    antigen presentation;    intestinal epithelial cells;    adaptive immunity;    Mouse;   

DOI  :  10.7554/eLife.72082

来源: eLife Sciences Publications, Ltd

【 摘 要 】

The innate immune system detects pathogens and initiates adaptive immune responses. Inflammasomes are central components of the innate immune system, but whether inflammasomes provide sufficient signals to activate adaptive immunity is unclear. In intestinal epithelial cells (IECs), inflammasomes activate a lytic form of cell death called pyroptosis, leading to epithelial cell expulsion and the release of cytokines. Here, we employed a genetic system to show that simultaneous antigen expression and inflammasome activation specifically in IECs is sufficient to activate CD8+ T cells. By genetic elimination of direct T cell priming by IECs, we found that IEC-derived antigens were cross-presented to CD8+ T cells. However, cross-presentation of IEC-derived antigen to CD8+ T cells only partially depended on IEC pyroptosis. In the absence of inflammasome activation, cross-priming of CD8+ T cells required Batf3+ dendritic cells (conventional type one dendritic cells [cDC1]), whereas cross-priming in the presence of inflammasome activation required a Zbtb46+ but Batf3-independent cDC population. These data suggest the existence of parallel inflammasome-dependent and inflammasome-independent pathways for cross-presentation of IEC-derived antigens.

【 授权许可】

CC BY