| Summary: | <p>Abstract</p> <p>Background</p> <p>Members of the CD36 scavenger receptor family have been implicated as sensors of microbial products that mediate phagocytosis and inflammation in response to a broad range of pathogens. We investigated the role of CD36 in host response to mycobacterial infection.</p> <p>Methods</p> <p>Experimental <it>Mycobacterium bovis </it>Bacillus Calmette-Guérin (BCG) infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, and <it>in vitro </it>co-cultivation of <it>M. tuberculosis</it>, BCG and <it>M. marinum </it>with <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/-</sup></it>murine macrophages.</p> <p>Results</p> <p>Using an <it>in vivo </it>model of BCG infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, we found that mycobacterial burden in liver and spleen is reduced (83% lower peak splenic colony forming units, p < 0.001), as well as the density of granulomas, and circulating tumor necrosis factor (TNF) levels in <it>Cd36<sup>-/- </sup></it>animals. Intracellular growth of all three mycobacterial species was reduced in <it>Cd36<sup>-/- </sup></it>relative to wild type <it>Cd36<sup>+/+ </sup></it>macrophages <it>in vitro</it>. This difference was not attributable to alterations in mycobacterial uptake, macrophage viability, rate of macrophage apoptosis, production of reactive oxygen and/or nitrogen species, TNF or interleukin-10. Using an <it>in vitro </it>model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination <it>in vivo </it>(i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within <it>Cd36<sup>-/- </sup></it>macrophages.</p> <p>Conclusions</p> <p>Together, these data indicate that CD36 deficiency confers resistance to mycobacterial infection. This observation is best explained by reduced intracellular survival of mycobacteria in the <it>Cd36<sup>-/- </sup></it>macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination.</p>
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