Exposure of BALB/c mice to low doses of Mycobacterium avium increases resistance to a subsequent high-dose infection.
BALB/c mice exposed intranasally (i.n.), intradermally (i.d.) or intraperitoneally (i.p.) to low doses of Mycobacterium avium (20 c.f.u. at three different times two weeks apart) showed an increased resistance to a subsequent high-dose (10(5) c.f.u.) infection. I.n.-exposed mice had few mycobacteria in the tissues (>100 c.f.u.) and showed an expansion of CD4(+) T cells associated with overproduction of IL-12 and IFN-gamma, but not IL-4 and IgG antibodies. Parenterally (i.p. and i.d.) exposed animals showed c.f.u. numbers higher than i.n.-exposed mice, together with overproduction of IL-12, IFN-gamma and IL-4 in the case of i.p.-exposed mice, and of IL-12, IFN-gamma and IgG2a and IgG1 antibodies in the case of i.d.-exposed mice. Low-dose exposures were not contained by athymic BALB/c nude mice; however, naive nude mice reconstituted with i.n.-primed CD4(+) T cells of BALB/c mice were protected against high-dose infection, indicating that CD4(+) T cells are essential to control even low-dose infections by M. avium. Overall, these data suggest that continuous i.n. exposure to M. avium doses commonly found in the environment may play a role in determining the natural resistance of normal hosts against this organism.
D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007121:Immunocompetence; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*