Importance of early gamma interferon production in Propionibacterium acnes-induced resistance to Toxoplasma gondii infection in mice.

Treatment of mice with heat-killed Propionibacterium (P.) acnes conferred transient protection against Toxoplasma infection. To investigate the mechanism of this nonspecific resistance, the production of gamma interferon (IFN-gamma) by P. acnes-injected mice was evaluated in comparison with that by noninjected controls upon infection with Toxoplasma. Mice pretreated with this bacterium produced significantly more IFN-gamma than that produced by control mice up to 24 hr of infection. A single injection of anti-IFN-gamma MAb on day 0 but not later than day 3 of infection resulted in a total abrogation of the resistance conferred by P. acnes. Likewise, daily injection of cyclosporin A (Cs-A), a potent inhibitor of T cell function, during the first 3 days of Toxoplasma infection severely exacerbated the infection, in accordance with a marked suppression of the early IFN-gamma production. In contrast, the administration of Cs-A for 3 consecutive days starting at day 4 had no significant consequence on P. acnes-induced anti-toxoplasma resistance, while it reduced greatly the ability of P. acnes-injected mice to produce IFN-gamma in the later phase of infection. Moreover, no significant increase in mortality and suppression of IFN-gamma production was noted in mice receiving anti-asialo GM1 antibody. These results suggest that the early IFN-gamma production by T cells is an essential event for the establishment of P. acnes-induced anti-toxoplasma resistance in mice.