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Exposure of BALB/c mice to low doses of Mycobacterium avium increases resistance to a subsequent high-dose infection

Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy¹

Author for correspondence: Dr Graziella Orefici. Tel: +39 06 49902333. Fax: +39 06 49387112. e-mail: gorefici{at}iss.it

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 (10⁵ 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-, 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- and IL-4 in the case of i.p.-exposed mice, and of IL-12, IFN- 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.

Keywords: intranasal low-dose exposure, intradermal low-dose exposure, intraperitoneal low-dose exposure, BALB/c nude mice, CD4⁺ T cells

Abbreviations: i.d., intradermal(ly); i.n., intranasal(ly); i.p., intraperitoneal(ly)

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