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Nlrp12 Mediates Adverse Neutrophil Recruitment during Influenza Virus Infection
Journal article   Peer reviewed

Nlrp12 Mediates Adverse Neutrophil Recruitment during Influenza Virus Infection

Emma E Hornick, Balaji Banoth, Ann M Miller, Zeb R Zacharias, Nidhi Jain, Mary E Wilson, Katherine N Gibson-Corley, Kevin L Legge, Gail A Bishop, Fayyaz S Sutterwala, …
The Journal of immunology (1950), Vol.200(3), pp.1188-1197
02/01/2018
DOI: 10.4049/jimmunol.1700999
PMCID: PMC5831365
PMID: 29282312

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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. 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. neutrophils and dendritic cells within the IAV-infected lungs produce less CXCL1 than their wild-type counterparts. Decreased CXCL1 production by dendritic cells was not due to a difference in CXCL1 protein stability, but instead to a decrease in 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.
Lung - pathology Dendritic Cells - immunology Mice, Inbred C57BL RNA, Messenger - genetics Neutrophils - immunology Male Chemokine CXCL1 - genetics RNA Stability - genetics Capillary Permeability - genetics Mice, Knockout Lung - virology Animals Orthomyxoviridae Infections - mortality Female Influenza A virus - immunology Mice Mice, Inbred BALB C Chemokine CXCL1 - metabolism Intracellular Signaling Peptides and Proteins - genetics Orthomyxoviridae Infections - virology Lung - immunology Orthomyxoviridae Infections - immunology Neutrophil Infiltration - immunology

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