Scavenger receptor A dampens induction of inflammation in response to the fungal pathogen Pneumocystis carinii.
Alveolar macrophages are the effector cells largely responsible for clearance of Pneumocystis carinii from the lungs. Binding of organisms to beta-glucan and mannose receptors has been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance of P. carinii, mice deficient in the expression of scavenger receptor A (SRA) were infected with P. carinii, and clearance of organisms was monitored over time. SRA-deficient (SRAKO) mice consistently cleared P. carinii 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 tumor necrosis factor alpha (TNF-alpha) than wild-type macrophages when stimulated with lipopolysaccharide in vitro but less TNF-alpha in response to P. carinii in vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF-alpha, interleukin 12 (IL-12), and IL-18 in response to P. carinii infection than did wild-type mice. Together, these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context of P. carinii infection.
Hollifield
Melissa
M
University of Kentucky Chandler Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA.
Bou Ghanem
Elsa
E
de Villiers
Willem J S
WJ
Garvy
Beth A
BA
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010587:Phagocytosis; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D039481:CD11b Antigen; D020382:Interleukin-18; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12