CD36 Deficiency Attenuates Experimental Mycobacterial Infection

BMC Infect Dis. 2010 Oct 15;10:299. doi: 10.1186/1471-2334-10-299.

Abstract

Background: 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.

Methods: Experimental Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection in Cd36+/+ and Cd36-/- mice, and in vitro co-cultivation of M. tuberculosis, BCG and M. marinum with Cd36+/+ and Cd36-/-murine macrophages.

Results: Using an in vivo model of BCG infection in Cd36+/+ and Cd36-/- 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 Cd36-/- animals. Intracellular growth of all three mycobacterial species was reduced in Cd36-/- relative to wild type Cd36+/+ macrophages in vitro. 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 in vitro model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination in vivo (i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within Cd36-/- macrophages.

Conclusions: 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 Cd36-/- macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • CD36 Antigens / deficiency*
  • CD36 Antigens / immunology
  • Cells, Cultured
  • Disease Models, Animal
  • Host-Pathogen Interactions*
  • Liver / microbiology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium Infections / immunology
  • Mycobacterium Infections / pathology*
  • Mycobacterium bovis / immunology
  • Mycobacterium bovis / pathogenicity*
  • Mycobacterium marinum / immunology
  • Mycobacterium marinum / pathogenicity*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity*
  • Spleen / microbiology
  • Virulence

Substances

  • CD36 Antigens