Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin.
Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial load. The ability of osteopontin to facilitate the clearance of mycobacteria was most pronounced early after infection and appeared to be independent of known mediators of resistance to infection by mycobacteria: antigen-specific T-cell immunity, gamma interferon production, and nitric oxide production. BCG grew more rapidly in macrophages derived from OPN-null mice than in those from wild-type mice, demonstrating that the null phenotype was due to an intrinsic macrophage defect. These results indicate that osteopontin augments the host response against a mycobacterial infection and that it acts independently from other antimycobacterial resistance mechanisms.
Nau
G J
GJ
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Liaw
L
L
Chupp
G L
GL
Berman
J S
JS
Hogan
B L
BL
Young
R A
RA
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006099:Granuloma / Q000209:etiology; D018960:Hyaluronan Receptors / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology*; D014498:Uracil / Q000378:metabolism
D016207:Cytokines; D018960:Hyaluronan Receptors; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D009569:Nitric Oxide; D014498:Uracil; D007371:Interferon-gamma