CXCL5 suppresses IL-17A mediated immunity during MRSA-induced pneumonia

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.114-114.7
• Main Authors: Ghimire, Laxman, Bergeron, Scott R., Paudel, Sagar, Jeyaseelan, Samithamby
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.114.7

Lipopolysaccharides induced CXC-chemokine (LIX or CXCL5) is a potent chemoattractant for neutrophil recruitment to the lung during acute bacterial infections. However, its role in MRSA-induced pneumonia has not been established. We used C57BL/6 (wild-type) and CXCL5 knockout (KO) mice to induce pneumonia by intratracheal inoculation of 5×107 colony forming units (CFUs) of MRSA per mouse. Mice were sacrificed at 12 and 24 hours post-infection to enumerate bacterial burden, determine cellular recruitment, and perform cytokine analysis. Flow cytometric analysis of lungs cells was performed to determine the source of IL-17A. Unlike their wild-type counterparts, KO mice were protected from MRSA-induced pneumonia having significantly higher survival and less bacterial burden in lung and BALF. Total leukocytes and neutrophil recruitment into the airspaces was significantly higher in KO mice. However, proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α were significantly higher in WT mice compared to that of KO mice. In contrast, IL-17A was significantly higher in KO mice. Blocking of IL-17A in the KO mice increased the bacterial burden in the lungs and BALF. In addition, pre-treatment of neutrophils with recombinant IL-17A significantly enhanced ROS production and killing ability of neutrophils in response to MRSA infection. Neutrophils and γδ-T cells were major sources of IL-17A during pulmonary MRSA infection. Together, our findings demonstrate that CXCL5 negatively regulates γδ-T cells and neutrophils driven IL-17A-mediated immunity during MRSA-induced pneumonia and blocking CXCL5 could be a potential therapeutic approach to treat MRSA-infected pneumonic patients.