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 ac...

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Bibliographic Details
Published in:eLife 2021-12, Vol.10
Main Authors: Deets, Katherine A, Nichols Doyle, Randilea, Rauch, Isabella, Vance, Russell E
Format: Article
Language:English
Subjects:
Adaptive immunity
Adaptive Immunity - immunology
Amino acids
Animals
Antigen presentation
Antigens
Apoptosis
Bacterial infections
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell activation
Cell death
Cross-Priming - immunology
Cytokines
Dendritic cells
Dendritic Cells - immunology
Epithelial cells
Epithelial Cells - immunology
Female
Immune system
Immunology and Inflammation
Infections
inflammasome
Inflammasomes
Inflammasomes - immunology
Innate immunity
intestinal epithelial cells
Intestinal Mucosa - cytology
Intestinal Mucosa - immunology
Lymphocytes
Lymphocytes T
Male
Mice
Mice, Transgenic
Pathogens
Proteins
Pyroptosis
Pyroptosis - immunology
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.72082