NRAMP-1 GENE ASSOCIATED WITH THE INDUCTION OF IMMUNE RESPONSES AND THE EXPRESSION OF RESISTANCE AGAINST MYCOBACTERIAL INFECTION

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The relationship between Nramp-lgene and cytokine production in murine mycobacteriosis was examined. C57BL/6 (NRAMP-1^s) and their Bcg congenic (NRAMP-1^r) mice were used in these studies. Initially the production of two cytokines- interleukin-10 (IL-10) and IL-12, which are secreted by macrophages after Mycobacterium (M).avium or M.tuberculosis stimulation, was examined. The cytokine profiles induced in the early phase of the M.avium infection were more distinct than those of M.tuberculosis. NRAMP-1^s macrophages produced higher level of IL-10 as compared with NRAMP-1^r macrophages when they were stimulated with M.avium. In contrast, lower level of IL-12 production was recognized in NRAMP-1^s as compared with NRAMP-1^r. Stimulation with M.tuberculosis failed to produce significant difference in the production of these two cytokines by the macrophages of both NRAMP-1^s and NRAMP-1^r. The effect of NRAMP-1 gene on the functions of natural killer (NK) cells in M.intracellulare-infected mice was also studied. Our results indicateded that NK cells might be a main source of IFN-γ production and contribute the induction of immune responses in M.intracellulare- infected mice despite their NRAMP-1 genotype.