MCP-1 plays a critical role in neutrophil function and pyroptosis during Carbapenemf-Resistant Klebsiella Pneumoniae

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.46-46.17
• Main Authors: Jin, Liliang, Ghimire, Laxman, Paudel, Sagar, Cai, Shanshan, Rangasamy, Tirumalai, Jeyaseelan, Samithamby
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.46.17

Monocyte chemoattractant protein-1 (MCP-1) is important for monocyte recruitment to the lungs in response to bacterial infection. MCP-1 is also essential for protective neutrophil recruitment to the lungs during Escherichia coli pneumoniae infection. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been rapidly growing as a life-threatening nosocomial disease in many countries. Little is known regarding the role of chemokines and early cellular immune responses in protective immunity to pulmonary infection with CRKP. In the current study, we investigated the role of MCP-1 in pulmonary innate immunity against CRKP infection in C57Bl/6 mice and MCP-1−/− mice. MCP-1 appears to be essential for restricting bacterial outgrowth and death in mice. Compared to the C57Bl/6 mice, MCP-1−/− mice showed reduced influx of neutrophils in the airways and lung parenchyma, as assessed by nucleated cell concentrations in BALF and myeloperoxidase activity (MPO) in lung tissue. Moreover, the neutrophil extracellular traps (NETs) induced by CRKP were reduced in MCP-1−/− mice in both in vitro and in vivo experiments. Intriguingly, subsequent to CRKP infection, MCP-1−/− mice demonstrated increased pyroptosis through higher expression of IL-1β and cleaved gasdermin-d in the lung. These findings enhance our understanding of the critical role of MCP-1 in modulating neutrophil function and pyroptosis in neutrophils and suggest that therapies targeting modulation of NETs and pyroptosis during CRKP infection should be explored.