LAUSR

Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation, increased infiltration by CD8+ T lymphocytes, and infection-driven exacerbations. Although cigarette smoke (CS) is the leading risk factor for COPD, the mechanisms driving development of COPD in only a subset of smokers are incompletely understood. Lung-resident mucosal-associated invariant T (MAIT) cells play a role in both microbial infections and inflammatory diseases. The role of MAIT cells in COPD pathology is unknown. Here, we examined MAIT cell activation in response to CS-exposed primary human bronchial epithelial cells (BEC) from healthy, COPD, or smoker donors. We observed significantly higher baseline MAIT cell responses to COPD BEC than healthy BEC. However, infected COPD BEC stimulated a smaller fold-increase in MAIT cell response despite increased microbial infection. For all donor groups, CS-exposed BEC elicited reduced MAIT cell responses; conversely, CS exposure increased ligand-mediated MR1 surface translocation in healthy and COPD BEC. Our data demonstrate MAIT cell activation is dysregulated in the context of CS and COPD. MAIT cells could contribute to CS- and COPD-associated inflammation through both inappropriate activation and reduced early recognition of bacterial infection, contributing to microbial persistence and COPD exacerbations.