Role of Innate-like Lymphocytes in the Pathogenesis of Community Acquired Pneumonia

Background: Mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of bacterial infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown. Methods: Using sputum samples from a well-characterised CAP cohort, MAIT cell (Vα7.2-Jα12/20/33) and Vδ2+ T cell (Vδ2-Jδ1/2/3/4) abundance was determined by quantitative PCR. Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and Vδ2+ T cells was inferred by 16S rRNA sequencing. Results: MAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and Vδ2+ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology, however there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon-α, and interferon- γ, and sputum neutrophil abundance, while Vδ2+ T cell abundance was associated with CXCL11 and interferon-γ. Conclusions: Pulmonary MAIT and Vδ2+ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.