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

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dc.contributor.authorSchäfer, Georgiaen_ZA
dc.contributor.authorGuler, Retoen_ZA
dc.contributor.authorMurray, Graemeen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorBrown, Gordon Den_ZA
dc.date.accessioned2015-11-23T12:35:21Z
dc.date.available2015-11-23T12:35:21Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationSchäfer, 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. <i>PLoS One</i>, http://hdl.handle.net/11427/15325en_ZA
dc.identifier.chicagocitationSchäfer, Georgia, Reto Guler, Graeme Murray, Frank Brombacher, and Gordon D Brown "The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/15325en_ZA
dc.identifier.citationSchäfer, 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.0008448en_ZA
dc.identifier.ris TY - Journal Article AU - Schäfer, Georgia AU - Guler, Reto AU - Murray, Graeme AU - Brombacher, Frank AU - Brown, Gordon D AB - 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. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0008448 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model TI - The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model UR - http://hdl.handle.net/11427/15325 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15325
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0008448
dc.identifier.vancouvercitationSchäfer G, Guler R, Murray G, Brombacher F, Brown GD. The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model. PLoS One. 2009; http://hdl.handle.net/11427/15325.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2009 Schäfer et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherCholesterolen_ZA
dc.subject.otherCell bindingen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherMycobacteriaen_ZA
dc.subject.otherLuciferaseen_ZA
dc.subject.otherCell binding assayen_ZA
dc.titleThe role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine modelen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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