Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with mycobacterium tuberculosis.
Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-gamma (IFN-gamma), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40(-/-) mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40(-/-) mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-gamma. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40(-/-) mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-gamma and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.
Cooper
A M
AM
Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.
Magram
J
J
Ferrante
J
J
Orme
I M
IM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis; D014376:Tuberculosis / Q000276:immunology*
D018664:Interleukin-12