The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model

 

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dc.contributor.author Schäfer, Georgia en_ZA
dc.contributor.author Guler, Reto en_ZA
dc.contributor.author Murray, Graeme en_ZA
dc.contributor.author Brombacher, Frank en_ZA
dc.contributor.author Brown, Gordon D en_ZA
dc.date.accessioned 2015-11-23T12:35:21Z
dc.date.available 2015-11-23T12:35:21Z
dc.date.issued 2009 en_ZA
dc.identifier.citation Schäfer, G., Guler, R., Murray, G., Brombacher, F., & Brown, G. D. (2009). The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model. PloS one, 4(12), e8448. doi:10.1371/journal.pone.0008448 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15325
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0008448
dc.description.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 . Methods and FINDINGS: 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, IFNγ, 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. CONCLUSION: 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Cholesterol en_ZA
dc.subject.other Cell binding en_ZA
dc.subject.other Macrophages en_ZA
dc.subject.other Alveolar macrophages en_ZA
dc.subject.other Mycobacteria en_ZA
dc.subject.other Luciferase en_ZA
dc.subject.other Cell binding assay en_ZA
dc.title The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2009 Schäfer et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.