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Title: Nlrp12 Mediates Adverse Neutrophil Recruitment during Influenza Virus Infection.

Authors: Hornick, Emma E; Banoth, Balaji; Miller, Ann M; Zacharias, Zeb R; Jain, Nidhi; Wilson, Mary E; Gibson-Corley, Katherine N; Legge, Kevin L; Bishop, Gail A; Sutterwala, Fayyaz S; Cassel, Suzanne L

Published In J Immunol, (2018 02 01)

Abstract: Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice. Nlrp12-/- neutrophils and dendritic cells within the IAV-infected lungs produce less CXCL1 than their wild-type counterparts. Decreased CXCL1 production by Nlrp12-/- dendritic cells was not due to a difference in CXCL1 protein stability, but instead to a decrease in Cxcl1 mRNA stability. Together, these data demonstrate a previously unappreciated role for Nlrp12 in exacerbating the pathogenesis of IAV infection through the regulation of CXCL1-mediated neutrophilic responses.

PubMed ID: 29282312 Exiting the NIEHS site

MeSH Terms: Animals; Capillary Permeability/genetics; Chemokine CXCL1/genetics; Chemokine CXCL1/metabolism*; Dendritic Cells/immunology; Female; Influenza A virus/immunology*; Intracellular Signaling Peptides and Proteins/genetics*; Lung/immunology; Lung/pathology; Lung/virology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration/immunology*; Neutrophils/immunology*; Orthomyxoviridae Infections/immunology*; Orthomyxoviridae Infections/mortality; Orthomyxoviridae Infections/virology; RNA Stability/genetics; RNA, Messenger/genetics

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