Regulation of interleukin-12 production in human cells stimulated with Mycobacterium bovis BCG.
Interleukin 12 (IL-12) is a monokine which plays a critical role in resistance to Mycobacterium tuberculosis infection. However, little is known about the regulation of IL-12 production by human cells stimulated with BCG. Here we report that in vitro infection of human mononuclear cells with M. bovis BCG induces the release of IL-12 protein. We also observed that the ability of BCG to stimulate release of IL-12 from human cells was significantly inhibited by IL-10. The inhibitory effect of IL-10 on the secretion of IL-12 was specific, as it was significantly abolished in the presence of anti-IL-10 neutralizing monoclonal antibody. These results were further confirmed as anti-IL-10 antibodies markedly increased the levels of IL-12, suggesting that BCG-induced IL-10, as well as exogenous IL-10, can regulate IL-12 production by human cells stimulated with M. bovis BCG. Interestingly, IFN-gamma production in response to BCG had no significant increase by the addition of neutralizing antibodies to IL-10. Moreover, anti-IL-12 antibodies markedly reduced the levels of IFN-gamma produced by BCG-stimulated human cells and abrogated the capacity of anti-IL-10 to increase BCG-induced IFN-gamma. These studies are the first to demonstrate a regulatory effect on IL-12 production by human cells infected with M. bovis BCG and at the same time suggest that IL-12 may play an essential role during the human immune response to M. bovis BCG stimulation.
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, México, D.F., 11340, México.
P
P
Méndez-Samperio
A
A
Trejo-Echeverria
H
H
Ayala-Verdin
D000906:Antibodies / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology
D000906:Antibodies; D001500:BCG Vaccine; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma