Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell derived antigen
- University of California, Berkeley, United States
- Oregon Health and Science University, United States
Abstract
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, 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 (cDC1), whereas cross-priming in the presence of pyroptosis required a Zbtb26+ but Batf3-independent cDC population. These data suggest the existence of parallel pyroptosis-dependent and pyroptosis-independent pathways for cross-presentation of IEC-derived antigens.
Data availability
Immunofluorescence images have been deposited in Dryad and can be found at https://doi.org/10.6078/D1ST46. All remaining data generated or analyzed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figures 1-6, Figure 3-figure supplement 1, Figure 4-figure supplement 1, Figure 5-figure supplement 1, Figure 5-figure supplement 4, Figure 6-figure supplement 2.
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Data from: Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell derived antigenDryad Digital Repository, doi:10.6078/D1ST46.
Article and author information
Author details
Funding
National Institutes of Health (AI075039)
- Russell E Vance
National Institutes of Health (AI063302)
- Russell E Vance
National Institutes of Health (AI155634)
- Russell E Vance
Howard Hughes Medical Institute (Investigator Award)
- Russell E Vance
National Institutes of Health (5T32GM007232)
- Katherine A Deets
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animal studies were approved by the UC Berkeley Animal Care and Use Committee (current protocol number: AUP-2014-09-6665-2).
Copyright
© 2021, Deets et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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