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

ABSTRACT: 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 ?? T cells in the clearance of P. aeruginosa lung infection is not yet well characterized. In this study, the role of ?? T cells was examined in an acute mouse model of P. aeruginosa lung infection. In the absence of ?? 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 ?? T cells, NKT cell-deficient mice exhibited wild-type level control of P. aeruginosa infection. Proinflammatory cytokines were also altered in ?? T cell-deficient mice, with increased production of interleukin-1?, interleukin-6, and tumor necrosis factor. ?? 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 ?? cell-deficient mice. These findings demonstrate that ?? 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.


PROVIDER: S-EPMC7240087 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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