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Mucosal Immunol. 2015 May;8(3):559-71. doi: 10.1038/mi.2014.88. Epub 2014 Oct 22.

Key role for scavenger receptor B-I in the integrative physiology of host defense during bacterial pneumonia.

Author information

1
Division of Intramural Research, Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
2
1] Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA [2] Integrated Laboratory Systems, Inc., National Institutes of Health, Research Triangle Park, North Carolina, USA.

Abstract

Scavenger receptor B-I (SR-BI) is a multirecognition receptor that regulates cholesterol trafficking and cardiovascular inflammation. Although it is expressed by neutrophils (PMNs) and lung-resident cells, no role for SR-BI has been defined in pulmonary immunity. Herein, we report that, compared with SR-BI(+/+) counterparts, SR-BI(-/-) mice suffer markedly increased mortality during bacterial pneumonia associated with higher bacterial burden in the lung and blood, deficient induction of the stress glucocorticoid corticosterone, higher serum cytokines, and increased organ injury. SR-BI(-/-) mice had significantly increased PMN recruitment and cytokine production in the infected airspace. This was associated with defective hematopoietic cell-dependent clearance of lipopolysaccharide from the airspace and increased cytokine production by SR-BI(-/-) macrophages. Corticosterone replacement normalized alveolar neutrophilia but not alveolar cytokines, bacterial burden, or mortality, suggesting that adrenal insufficiency derepresses PMN trafficking to the SR-BI(-/-) airway in a cytokine-independent manner. Despite enhanced alveolar neutrophilia, SR-BI(-/-) mice displayed impaired phagocytic killing. Bone marrow chimeras revealed this defect to be independent of the dyslipidemia and adrenal insufficiency of SR-BI(-/-) mice. During infection, SR-BI(-/-) PMNs displayed deficient oxidant production and CD11b externalization, and increased surface L-selectin, suggesting defective activation. Taken together, SR-BI coordinates several steps in the integrated neutrophilic host defense response to pneumonia.

PMID:
25336169
PMCID:
PMC4406784
DOI:
10.1038/mi.2014.88
[Indexed for MEDLINE]
Free PMC Article

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