Bystander Activation of Pulmonary Trm Cells Attenuates the Severity of Bacterial Pneumonia by Enhancing Neutrophil Recruitment

Tissue-resident memory T (Trm) cells are described as having a “sensing and alarming” function, meaning they can rapidly release cytokines in response to local cognate antigen recognition, which in turn, draws circulating immune cells into the tissue. Here, we show noncognate, bystander activation can also trigger the sensing and alarming function of pulmonary CD8+ Trm cells. Virus-specific CD8+ Trm cells lodged in the lung parenchyma, but not memory CD8+ T cells located in the vasculature, rapidly synthesize interferon γ (IFN-γ) following the inhalation of heat-killed bacteria or bacterial products, a process driven by interleukin-12 (IL-12)/IL-18 exposure. We show that a respiratory bacterial infection leads to bystander activation of lung Trm cells that boosts neutrophil recruitment into the airways and attenuates the severity of bacterial pneumonia. These data reveal that lung Trm cells have innate-like properties, enabling amplification of inflammation and participation in noncognate responses to bacterial infections. [Display omitted] •Lung Trm cells undergo bystander activation following exposure to bacterial products•IL-12/IL-18 exposure triggers bystander activation of lung Trm cells•Bystander-activated lung Trm cells enhance neutrophil recruitment into the airways Ge et al. show that lung tissue-resident memory T (Trm) cells undergo bystander activation in response to bacterial products. This boosts neutrophil recruitment into the airways and attenuates the severity of bacterial pneumonia. Lung Trm cells have innate-like properties, amplifying inflammation and participating in noncognate memory T cell responses to bacterial infections.