title: The scavenger receptor CD36 downmodulates the early inflammatory response while enhancing bacterial phagocytosis during pneumococcal pneumonia.
abstract: CD36 is a scavenger receptor that exhibits pleiotropic functions, including adhesion to thrombospondin, inhibition of angiogenesis, transport of long-chain fatty acids, and clearance of apoptotic cells. In addition, it has been implicated in the host immune response because it acts as a coreceptor for TLR2 and plays a role in Staphylococcus aureus infection. However, its role in other Gram-positive bacterial infections is unclear. In this study, using mice deficient in CD36, we sought to examine the role of CD36 in pneumococcal pneumonia, a major cause of morbidity and mortality worldwide. We show that CD36 is expressed on both alveolar macrophages and respiratory epithelial cells. Early in infection, CD36(-/-) mice have an exaggerated inflammatory response compared with wild-type littermate controls. In vitro studies using CD36(-/-) primary cells confirm the enhanced early inflammation in response to S. pneumoniae and its lipoteichoic acid, demonstrate that S. pneumoniae binds to cells via its phosphocholine residues, and suggest a role for CD36 in reducing inflammation induced by the phosphocholine residues of pneumococcal lipoteichoic acid. Later in infection, although CD36(-/-) mice exhibit impaired bacterial clearance, owing to a decreased capacity of CD36(-/-) macrophages to phagocytose S. pneumoniae, minor effects on mortality occur, in comparison with those in wild-type littermate control mice. These data show that CD36 contributes to the pulmonary host response during S. pneumoniae infection by virtue of its ability to act as a phagocytic receptor and as a modulator of the early innate immune response.
authors.affiliation: Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Omar
authors.initials: O
authors.lastname: Sharif
authors.forename: Ulrich
authors.initials: U
authors.lastname: Matt
authors.forename: Simona
authors.initials: S
authors.lastname: Saluzzo
authors.forename: Karin
authors.initials: K
authors.lastname: Lakovits
authors.forename: Isabella
authors.initials: I
authors.lastname: Haslinger
authors.forename: Tanja
authors.initials: T
authors.lastname: Furtner
authors.forename: Bianca
authors.initials: B
authors.lastname: Doninger
authors.forename: Sylvia
authors.initials: S
authors.lastname: Knapp
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology*
chemical_list: D018955:CD36 Antigens; D010767:Phosphorylcholine