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Macrophage scavenger receptor MARCO modulates early events in innate immunity against Influenza
Author(s) -
Ghosh Sanjukta,
Kobzik Lester
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb712
Subject(s) - neutrophilia , scavenger receptor , proinflammatory cytokine , immunology , influenza a virus , inflammation , biology , virus , macrophage , innate immune system , immunity , immune system , in vitro , virology , endocrinology , lipoprotein , biochemistry , cholesterol
We investigated the role of MARCO against infection with influenza A virus (IAV). In vitro infection of MARCO−/− or WT macrophages with IAV showed no significant difference in virus uptake. However, MARCO−/− mice had increased PMNs in the lungs early after infection compared to wild‐type controls accompanied with greater induction of acute inflammatory cytokines investigated at day 2 and lower viral M1 gene expression at day 4, post infection. Experimental enhancement of the early inflammatory response in infected WT mice by aerosol exposure to LPS (200 ng/ml, 20 minutes) 12 h after IAV challenge resulted in much lower viral M1 gene expression in the lungs in 2 days, suggesting that inflammatory cellular influx early during infection helps to suppress viral outgrowth. Notably, the MARCO−/− mice showed greater survival following low dose viral challenge than the WT (67% vs 34%, N=10 per group) without showing appreciable difference in T lymphocyte numbers. We hypothesized that accumulation of oxidized proinflammatory lipoproteins in lungs in absence of its scavenger MARCO, could trigger increased neutrophilia. BAL of infected MARCO−/− animals showed 2‐fold greater oxidized lipoproteins accumulation early after infection. The data suggest that MARCO clearance of inflammatory intermediates during influenza acts to reduce an early inflammatory response, which is beneficial for viral clearance and recovery from influenza. NIH Grant ES011008‐08 ES 00002