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

Georgia Schäfer, Reto Guler, Graeme Murray, Frank Brombacher, Gordon D Brown

Research output: Contribution to journalArticle

43 Citations (Scopus)
3 Downloads (Pure)

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, 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. 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.
Original languageEnglish
Article numbere8448
Number of pages13
JournalPloS ONE
Volume4
Issue number12
DOIs
Publication statusPublished - 24 Dec 2009

Fingerprint

Class B Scavenger Receptors
Scavenger Receptors
Mycobacterium tuberculosis
animal models
receptors
Infection
infection
Mycobacterium
Macrophages
Pathogens
macrophages
CD36 Antigens
Lipoprotein Receptors
Cholesterol
Dietary Cholesterol
Lung
Disease Resistance
Cholesterol Esters
mice
cholesterol

Keywords

  • animals
  • bacterial adhesion
  • cell line
  • cells, cultured
  • cholesterol
  • disease models, animal
  • mice
  • Mycobacterium bovis
  • Mycobacterium tuberculosis
  • protein binding
  • rats
  • scavenger receptors, class B
  • transfection
  • tuberculosis

Cite this

The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model. / Schäfer, Georgia; Guler, Reto; Murray, Graeme; Brombacher, Frank; Brown, Gordon D.

In: PloS ONE, Vol. 4, No. 12, e8448, 24.12.2009.

Research output: Contribution to journalArticle

@article{cf90df9785e74c208a7d9566311d482e,
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. 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, 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. 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.",
keywords = "animals, bacterial adhesion, cell line, cells, cultured, cholesterol, disease models, animal, mice, Mycobacterium bovis, Mycobacterium tuberculosis, protein binding, rats, scavenger receptors, class B, transfection, tuberculosis",
author = "Georgia Sch{\"a}fer and Reto Guler and Graeme Murray and Frank Brombacher and Brown, {Gordon D}",
year = "2009",
month = "12",
day = "24",
doi = "10.1371/journal.pone.0008448",
language = "English",
volume = "4",
journal = "PloS ONE",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "12",

}

TY - JOUR

T1 - The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model

AU - Schäfer, Georgia

AU - Guler, Reto

AU - Murray, Graeme

AU - Brombacher, Frank

AU - Brown, Gordon D

PY - 2009/12/24

Y1 - 2009/12/24

N2 - 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, 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. 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.

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, 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. 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.

KW - animals

KW - bacterial adhesion

KW - cell line

KW - cells, cultured

KW - cholesterol

KW - disease models, animal

KW - mice

KW - Mycobacterium bovis

KW - Mycobacterium tuberculosis

KW - protein binding

KW - rats

KW - scavenger receptors, class B

KW - transfection

KW - tuberculosis

U2 - 10.1371/journal.pone.0008448

DO - 10.1371/journal.pone.0008448

M3 - Article

VL - 4

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 12

M1 - e8448

ER -