title: CD36-Mediated Uptake of Surfactant Lipids by Human Macrophages Promotes Intracellular Growth of Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis imposes a large global health burden as the airborne agent of tuberculosis. Mycobacterium tuberculosis has been flourishing in human populations for millennia and is therefore highly adapted to the lung environment. Alveolar macrophages, a major host cell niche for M. tuberculosis, are not only phagocytose inhaled microbes and particulate matter but are also crucial in catabolizing lung surfactant, a lipid-protein complex that lines the alveolar spaces. Because macrophage host defense properties can be regulated by surfactant and M. tuberculosis can use host lipids as a carbon source during infection, we sought to determine the receptor(s) involved in surfactant lipid uptake by human macrophages and whether the presence of those lipids within macrophages prior to infection with M. tuberculosis enhances bacterial growth. We show that preformed scavenger receptor CD36 is redistributed to the cell membrane following exposure to surfactant lipids and surfactant protein A. Subsequently, surfactant lipids and/or surfactant protein A enhance CD36 transcript and protein levels. We show that CD36 participates in surfactant lipid uptake by human macrophages, as CD36 knockdown reduces uptake of dipalmitoylphosphatidylcholine, the most prevalent surfactant lipid species. Finally, exposing human macrophages to surfactant lipids prior to infection augments M. tuberculosis growth in a CD36-dependent manner. Thus, we provide evidence that CD36 mediates surfactant lipid uptake by human macrophages and that M. tuberculosis exploits this function for growth.
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, OH 43210; and.|The Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Dodd
authors.affiliation: The Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210.
authors.forename: Charlie J
authors.identifier: 0000-0002-6355-0638
authors.initials: CJ
authors.lastname: Pyle
authors.affiliation: The Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210.
authors.forename: Rebecca
authors.identifier: 0000-0003-2749-2044
authors.initials: R
authors.lastname: Glowinski
authors.affiliation: The Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210.
authors.forename: Murugesan V S
authors.identifier: 0000-0002-1515-1122
authors.initials: MV
authors.lastname: Rajaram
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus, OH 43210; and larry.schlesinger@osumc.edu.|The Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D042541:Intracellular Space / Q000382:microbiology*; D050356:Lipid Metabolism; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D010587:Phagocytosis; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D018955:CD36 Antigens; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants; D034741:RNA, Small Interfering; D015060:1,2-Dipalmitoylphosphatidylcholine