title: The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model.
abstract: BACKGROUND
  The interaction between Mycobacterium tuberculosis (Mtb) and host cells is complex and far from being understood. The role of the different receptor(s) implicated in the recognition of Mtb in particular remains poorly defined, and those that have been found to have activity in vitro were subsequently shown to be redundant in vivo.
  
  
  RESULTS
  To identify novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA library and identified scavenger receptor B class 1 (SR-B1) as a receptor for mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol, and has also recently been implicated in the recognition of other pathogens. We show here that mycobacteria can bind directly to SR-B1 on transfected cells, and that this interaction could be inhibited in the presence of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage populations, including alveolar macrophages, that express this receptor, however, no differences in the recognition and response to mycobacteria were observed in macrophages isolated from SR-B1(-/-) or wild type mice in vitro. Moreover, when wild type and SR-B1(-/-) animals were infected with a low dose of Mtb (100 CFU/mouse) there were no alterations in survival, bacterial burdens, granuloma formation or cytokine production in the lung. However, significant reduction in the production of TNF, IFNgamma, and IL10 were observed in SR-B1(-/-) mice following infection with a high dose of Mtb (1000 CFU/mouse), which marginally affected the size of inflammatory foci but did not influence bacterial burdens. Deficiency of SR-B1 also had no effect on resistance to disease under conditions of varying dietary cholesterol. We did observe, however, that the presence of high levels of cholesterol in the diet significantly enhanced the bacterial burdens in the lung, but this was independent of SR-B1.
  
  
  CONCLUSIONS
  SR-B1 is involved in mycobacterial recognition, but this receptor plays only a minor role in anti-mycobacterial immunity in vivo. Like many other receptors for these pathogens, the loss of SR-B1 can be functionally compensated for under normal conditions.
authors.affiliation: Division of Immunology, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Georgia
authors.initials: G
authors.lastname: Schäfer
authors.forename: Reto
authors.initials: R
authors.lastname: Guler
authors.forename: Graeme
authors.initials: G
authors.lastname: Murray
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D009163:Mycobacterium bovis / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000172:deficiency / Q000378:metabolism*; D014162:Transfection; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology
chemical_list: C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol