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

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 are cross-presented to
CD8+ T cells. However, activation of CD8+ T cells by
IEC-derived antigen only partially depended on IEC pyroptosis. In the
absence of inflammasome activation, cross-priming of CD8+ T cells
required Batf3+ dendritic cells (cDC1), whereas
cross-priming in the presence of pyroptosis required
a Batf3-independent cDC population. These data suggest the
existence of parallel pyroptosis-dependent and pyroptosis-independent but
cDC1-dependent pathways for cross-presentation of IEC-derived antigens.