Mice lacking the multidrug resistance protein 1 have a transiently impaired immune response during tuberculosis.
A T helper (Th) 1 immune response is important for host defense against tuberculosis. The multidrug resistance protein (Mrp) 1 is constitutively present at low levels on Th2 lymphocytes, and is expressed on Th1 lymphocytes upon activation. To determine the role of Mrp1 in the pathogenesis of tuberculosis, Mrp1 deficient (-/-) and normal wild type mice were intranasally infected with Mycobacterium tuberculosis. At 2 weeks after infection, Mrp1(-/-) mice had reduced levels of the Th1 cytokine interferon-gamma and an impaired granuloma formation in their lungs. At 5 weeks postinfection, M. tuberculosis outgrowth was enhanced in lungs and livers of Mrp1(-/-) mice. A more prolonged observation of these mice, up to 4 months, revealed no differences in survival or mycobacterial outgrowth. These data suggest that Mrp1 plays an early but dispensable role in the protective immune response to pulmonary tuberculosis.
Verbon
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Department of Infectious Diseases, Tropical Medicine and AIDS, Laboratory of Experimental Internal Medicine and Department of Pathology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. A.Verboon@amc.uva.nl
Leemans
J C
JC
Weijer
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S
Florquin
S
S
Van Der Poll
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000281:Administration, Intranasal; D000818:Animals; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D014375:Tuberculoma / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007371:Interferon-gamma