Mice Lacking γδ T Cells Exhibit Impaired Clearance of Pseudomonas aeruginosa Lung Infection and Excessive Production of Inflammatory Cytokines

Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic and life-threatening infections in immunocompromised patients. A better understanding of the role that innate immunity plays in the control of P. aeruginosa infection is crucial for therapeutic development. Specifically, the role of unconventional immune cells like gamma delta T cells in the clearance of P. aeruginosa lung infection is not yet well characterized. In this study, the role of gamma delta T cells was examined in an acute mouse model of P. aeruginosa lung infection. In the absence of gamma delta T cells, mice displayed impaired bacterial clearance and decreased survival, outcomes which were associated with delayed neutrophil recruitment and impaired recruitment of other immune cells (macrophages, T cells, natural killer cells, and natural killer T [NKT] cells) into the airways. Despite reduced NKT cell recruitment in the airways of mice lacking gamma delta T cells, NKT cell-deficient mice exhibited wild-type level control of P. aeruginosa infection. Proinflammatory cytokines were also altered in gamma delta T cell-deficient mice, with increased production of interleukin-1 beta, interleukin-6, and tumor necrosis factor. gamma delta T cells did not appear to contribute significantly to the production of interleukin-17A or the chemokines CXCL1 and CXCL2. Importantly, host survival could be improved by inhibiting tumor necrosis factor signaling with the soluble receptor construct etanercept in gamma delta cell-deficient mice. These findings demonstrate that gamma delta T cells play a protective role in coordinating the host response to P. aeruginosa lung infection, both in contributing to early immune cell recruitment and by limiting inflammation.