Research Article: The Role of Scavenger Receptor B1 in Infection with Mycobacterium tuberculosis in a Murine Model

Date Published: December 24, 2009

Publisher: Public Library of Science

Author(s): Georgia Schäfer, Reto Guler, Graeme Murray, Frank Brombacher, Gordon D. Brown, Ludovic Tailleux. http://doi.org/10.1371/journal.pone.0008448

Abstract: 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.

Partial Text: Tuberculosis is the leading cause of death worldwide from a single infectious disease. The causative agent, Mycobacterium tuberculosis (Mtb), enters the host typically via aerosols, and alveolar macrophages are considered the first cells to engulf Mtb and become infected. Although the initial interaction of the pathogen with the host macrophage is considered a critical step in the pathogenesis of Mtb, the role of the receptors that play a role in mediating the entry of Mtb into macrophages and in transducing intracellular signals is very controversial and far from being understood. Over the years, more than a dozen receptors have been shown to recognize and bind mycobacteria (reviewed in [1]). However, the role of these receptors has been mostly based on in vitro examination in transfected cells; studies using inhibitors or animals deficient for specific receptors have indicated that these receptors are dispensable [2]–[7]. Since no direct functional-based search for the macrophage receptors involved in mycobacterial recognition has been performed, here we utilised a generalized screening method [8] with which we identified scavenger receptor B class 1 (SR-B1) as a novel macrophage receptor involved in the recognition of Mtb.

The identification of host pattern recognition receptors that recognise Mtb represents a potential opportunity for anti-mycobacterial prophylaxis, as the interruption of binding may functionally disrupt Mtb entry into its host cell niche. By screening a retroviral cDNA expression library derived from RAW264.7 murine macrophages, we identified SR-B1 as a receptor for mycobacteria (Fig. 1A and B). As a member of the CD36 family of scavenger receptors, which have been well described for their function in cholesterol metabolism, we show here that SR-B1 is also involved in mycobacterial recognition. To our knowledge, this activity so far has only been attributed to the Drosophila homologue Pes [19].

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http://doi.org/10.1371/journal.pone.0008448

 

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