Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling

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 T(H)1 and T(H)17 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 T(H)17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with T(H)1 cells, and T(H)17 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.

Automated summary

A vaccine composed of OmpX from Klebsiella pneumoniae and LTA1 adjuvant administered intrapulmonary can induce T(H)1 and T(H)17 cells that share transcriptional features with cells elicited by heat-killed K. pneumoniae, showing promising results in promoting immunity to K. pneumoniae.