Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States.
Elife. 2021 Dec 23;10:e72082. doi: 10.7554/eLife.72082.
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 dendritic cells (conventional type one dendritic cells [cDC1]), whereas cross-priming in the presence of inflammasome activation required a but -independent cDC population. These data suggest the existence of parallel inflammasome-dependent and inflammasome-independent pathways for cross-presentation of IEC-derived antigens.
先天免疫系统可识别病原体并启动适应性免疫应答。炎性小体是先天免疫系统的核心组成部分，但炎性小体是否能提供足够的信号来激活适应性免疫尚不清楚。在肠道上皮细胞（IECs）中，炎性小体激活一种称为细胞焦亡的裂解形式的细胞死亡，导致上皮细胞排出和细胞因子释放。在这里，我们采用遗传系统表明，同时在 IECs 中表达抗原和激活炎性小体足以激活 CD8 T 细胞。通过遗传消除 IEC 对 T 细胞的直接启动，我们发现 IEC 衍生的抗原被交叉呈递给 CD8 T 细胞。然而，IEC 衍生抗原向 CD8 T 细胞的交叉呈递仅部分依赖于 IEC 的细胞焦亡。在没有炎性小体激活的情况下，CD8 T 细胞的交叉呈递需要树突状细胞（传统的 1 型树突状细胞[cDC1]），而在存在炎性小体激活的情况下，需要一种依赖 but 的 cDC 群体。这些数据表明，IEC 衍生抗原的交叉呈递存在平行的炎性小体依赖和炎性小体非依赖途径。
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