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 ha...

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Bibliographic Details
Published in:Infection and immunity 1999-08, Vol.67 (8), p.4223-4230
Main Authors: NAU, G. J, LIAW, L, CHUPP, G. L, BERMAN, J. S, HOGAN, B. L. M, YOUNG, R. A
Format: Article
Language:English
Subjects:
Animals
Bacterial diseases
Bacteriology
Biological and medical sciences
Cytokines - physiology
Experimental bacterial diseases and models
Fundamental and applied biological sciences. Psychology
Granuloma - etiology
Host Response and Inflammation
Hyaluronan Receptors - physiology
Infectious diseases
Interferon-gamma - biosynthesis
Macrophages - physiology
Medical sciences
Mice
Microbiology
Mycobacterium bovis
Nitric Oxide - metabolism
Osteopontin
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Sialoglycoproteins - genetics
Sialoglycoproteins - physiology
Tuberculosis - immunology
Uracil - metabolism
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Summary: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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.67.8.4223-4230.1999