Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling
- 10 September 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 6 (63), eabf1198
- https://doi.org/10.1126/sciimmunol.abf1198
Abstract
Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both TH1 and TH17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae. Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4+ T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4+ T cells from OmpX+LTA1–immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited TH17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with TH1 cells, and TH17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a promising vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.Keywords
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