Enhanced macrophage activity in granulomatous lesions of immune mice challenged with Mycobacterium tuberculosis.
In this study, we evaluated the cellular influx and cytokine environment in the lungs of mice made immune by prior vaccination with Mycobacterium bovis bacillus Calmette-Guérin compared with control mice after infection with Mycobacterium tuberculosis to characterize composition of protective lesions in the lungs. Immune mice controlled the growth of the M. tuberculosis challenge more efficiently than control mice. In immune animals, granulomatous lesions were smaller and had a more lymphocytic core, less foamy cells, less parenchymal inflammation, and slower progression of lung pathology than in lungs of control mice. During the chronic stage of the infection, the bacterial load in the lungs of immune mice remained at a level 10 times lower than control mice, and this was associated with reduced numbers of CD4P(+P) and CD8P(+P) T cells, and the lower expression of protective (IL-12, IFN-gamma), inflammatory (TNF-alpha), immunoregulatory (GM-CSF), and immunosuppressive (IL-10) cytokines. The immune mice had higher numbers of CD11b- CD11c(high) DEC-205(low) alveolar macrophages, but lower numbers of CD11b+ CD11c(high) DEC-205(high) dendritic cells, with the latter expressing significantly lower levels of the antiapoptotic marker TNFR-associated factor-1. Moreover, during the early stage of chronic infection, lung dendritic cells from immune mice expressed higher levels of MHC class II and CD40 molecules than similar cells from control mice. These results indicate that while a chronic disease state is the eventual outcome in both control and immune mice infected with M. tuberculosis by aerosol exposure, immune mice develop a protective granulomatous lesion by increasing macrophage numbers and reduced expression of protective and inflammatory cytokines.
Ordway
Diane
D
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. dordway@lamar.colostate.edu
Harton
Marisa
M
Henao-Tamayo
Marcela
M
Montoya
Rose
R
Orme
Ian M
IM
Gonzalez-Juarrero
Mercedes
M
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage; D019013:CD40 Antigens / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D047990:TNF Receptor-Associated Factor 1 / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
D001500:BCG Vaccine; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D047990:TNF Receptor-Associated Factor 1