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Infect. Immun. doi:10.1128/IAI.00393-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Scavenger receptor A dampens induction of inflammation in response to the fungal pathogen Pneumocystis

Departments of Microbiology, Immunology, and Molecular Genetics and Internal Medicine Divisions of Infectious Diseases and Digestive Diseases and Nutrition, University of Kentucky Chandler Medical Center, and Lexington Veteran's Administration Medical Center, Lexington, KY 40536

^* To whom correspondence should be addressed. Email: bgarv0{at}uky.edu.

	Abstract

Alveolar macrophages are the effector cells largely responsible for clearance of Pneumocystis (PC) from the lungs. Binding of organisms to -glucan and mannose receptors have been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance of PC, mice deficient in expression of Scavenger Receptor A (SRA) were infected with PC and clearance of organisms followed over time. SR-A deficient mice (SRAKO) consistently cleared PC faster than did wild type control mice. Expedited clearance corresponded to elevated numbers of activated CD4⁺ T cells in the alveolar spaces of SRAKO mice compared to wild type mice. Alveolar macrophages from SRAKO mice had increased expression of CD11b on their surfaces consistent with an activated phenotype. However, they were not more phagocytic than macrophages expressing SRA as measured by an in vivo phagocytosis assay. SRAKO alveolar macrophages produced significantly more TNF than wild type macrophages when stimulated with LPS in vitro but less TNF in response to PC in vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF, IL-12, and IL-18 in response to PC infection than did wild type mice. Together these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context of PC infection.