Osteopontin is not crucial to protective immunity during murine tuberculosis.
Upon infection with Mycobacterium (M.) tuberculosis, the development of a strong T helper 1 (Th1)-mediated adaptive immune response is considered as being most important for containment of the infection. Osteopontin (OPN) is a phosphorylated glycoprotein that is chemotactic for inflammatory cells and has been implicated in the induction of Th1 responses and granulomatous disease. We tested the hypothesis that OPN facilitates protective immunity during M. tuberculosis infection using wild-type (WT) and OPN knockout (KO) mice in a model of pulmonary tuberculosis. OPN expression was up-regulated in alveolar macrophages and lymphoid cells during M. tuberculosis infection. There were no significant differences in bacterial outgrowth, inflammation or recruitment of lymphocytes, macrophages and polymorphonuclear cells in the lungs after 2 and 5 weeks of infection. However, the numbers of CD4(+) and CD8(+) T cells were reduced in the absence of OPN 5 weeks after infection. Similar concentrations of cytokine were observed in lungs from both WT mice and OPN KO mice; however, there was a trend towards decreased levels of interferon-gamma (IFN-gamma) in OPN KO mice 5 weeks after infection. Despite an unaltered immune response in the early phase of tuberculosis, OPN KO mice had a modest survival advantage. Of note, both pulmonary bacterial loads and lung inflammation were reduced in these mice 31 weeks after infection. These data suggest that OPN is not crucial for protective immunity upon M. tuberculosis infection and during the late phase of tuberculosis may even be detrimental for the host.
van der Windt
Gerritje J W
GJ
Center of Infection and Immunity Amsterdam (CINIMA), Amsterdam, the Netherlands. g.j.vanderwindt@amc.uva.nl
Wieland
Catharina W
CW
Wiersinga
Willem J
WJ
Florquin
Sandrine
S
van der Poll
Tom
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D014373:Tuberculin / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
D014373:Tuberculin; D053495:Osteopontin; D007371:Interferon-gamma