CD36 deficiency attenuates experimental mycobacterial infection.
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.
Institute of Medical Sciences, University of Toronto, Toronto, Canada.
Michael
M
Hawkes
Xiaoming
X
Li
Maryanne
M
Crockett
Angelina
A
Diassiti
Constance
C
Finney
Gundula
G
Min-Oo
W Conrad
WC
Liles
Jun
J
Liu
Kevin C
KC
Kain
D000818:Animals; D058491:Bacterial Load; D018955:CD36 Antigens / Q000172:deficiency* / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000276:immunology / Q000473:pathology*; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity*; D019910:Mycobacterium marinum / Q000276:immunology / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology; D014774:Virulence
D018955:CD36 Antigens