In mice infected with a sublethal dose of Salmonella typhimurium, the injection of an anti-gamma interferon (IFN-gamma) monoclonal antibody increased bacterial proliferation in the spleen and led to death on day 7 or 8. Depletion of both CD4+ and CD8+ T cells with monoclonal antibodies in vivo had a much less marked effect during the first week of infection than the administration of anti-IFN-gamma antibodies, suggesting that cells other than T lymphocytes participate in the production of IFN-gamma at this time. Administration of anti-tumor necrosis factor alpha (TNF-alpha) antibodies to mice infected with a sublethal dose of S. typhimurium induced the same effect as anti-IFN-gamma antibodies, while the administration of both antibodies resulted in a synergistic interaction. When mice were infected with an avirulent strain of S. typhimurium and challenged on day 7 either with a virulent strain of S. typhimurium or with Listeria monocytogenes, their resistance to reinfection was slightly depressed by anti-IFN-gamma or anti-TNF-alpha antibodies given 1 day before challenge and much more strongly depressed by the simultaneous administration of both antibodies. Taken together, these results indicate that IFN-gamma and TNF-alpha play an essential role in acquired resistance during the early phase of S. typhimurium infection.

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Previous studies have shown that gamma interferon (IFN-␥) plays a major role in natural resistance to Salmonella typhimurium during the early phase of infection. To assess whether the level of natural resistance in mice is related to the level of IFN-␥ gene expression, we compared IFN-␥ mRNA levels by means of reverse transcriptase-PCR in the spleens of genetically susceptible Ity s (C57BL/6 and BALB/c) and resistant Ity r (CBA and DBA/2) mice during the first 5 days of infection. The mRNA expression of interleukin-10 (IL-10), a cytokine which antagonizes IFN-␥ effects, was also investigated. Mice were infected with 10 3 CFU of the virulent strain S. typhimurium C5, a dose which is lethal within a week for susceptible mice only. IFN-␥ mRNA increased to similar levels in both susceptible and resistant mice, suggesting that susceptibility to S. typhimurium infection is not related to defective IFN-␥ gene expression. In contrast, IL-10 mRNA reached much higher levels in susceptible than in resistant mice. Similar results were found in Ity congenic mice, confirming a link between the presence of the Ity s allele and a high level of IL-10 gene expression during infection. High levels of IL-10 mRNA in susceptible mice correlated with high IL-10 serum levels (on day 5), whereas IL-10 was not detectable in the sera of resistant mice. However, administration of neutralizing anti-IL-10 monoclonal antibodies did not modify the course of infection. To evaluate the influence of bacterial multiplication on IL-10 mRNA expression, susceptible mice were infected with an attenuated strain of S. typhimurium. This strain induced a low level of IL-10 mRNA expression. When susceptible mice were immunized with an attenuated strain and challenged with the virulent strain, they inhibited the growth of the challenge bacteria and exhibited a low level of IL-10 mRNA. In contrast, when resistant mice were infected with a high (lethal) dose of the virulent strain, they exhibited a high level of IL-10 mRNA. Taken together, these results indicate that the level of IL-10 gene expression correlates with the level of bacterial multiplication in the organs and that the high level of IL-10 mRNA in Ity s mice is a consequence rather than the cause of their susceptibility to S. typhimurium infection. Salmonella typhimurium is a facultative intracellular bacterium which can enter and multiply within macrophages and also nonphagocytic cells (18). During experimental infection in mice, the bacteria replicate mainly in the spleen and liver and induce a disease similar to human typhoid fever. Following intravenous challenge, acquired immunity to mouse salmonellosis is mainly T cell mediated, with the participation of both CD4 ϩ and CD8 ϩ subpopulations (21, 28). The antibody response also contributes to acquired immunity (11, 20). The survival of animals before the development of specific acquired immunity depends on natural resistance. Natural resistance to S. typhimurium infection in mice is regulated by several genes (30), in particular Ity, which contr...

Rhodococcus equi, a facultative intracellular gram-positive bacterium, can induce life-threatening infections in immunocompromised patients, especially those with AIDS. We have studied the mechanism of acquired immunity to this pathogen in a murine model. Protective immunity was induced by live but not killed bacteria. Adoptive transfer of resistance was obtained with spleen cells but not immune serum from mice immunized intravenously 30 days earlier with live bacteria. In normal mice, an intravenous challenge of 5 x 10(6) CFU of R. equi was cleared from the spleen, liver, and lungs within 3 weeks, whereas athymic nude mice were unable to clear the bacteria. In vivo depletion with monoclonal antibodies showed that both CD4+ and CD8+ T-cell subsets participate in the clearance of bacteria and that CD8+ T cells play the major role.

Arbitrarily primed PCR with three primers and pulsed-field gel electrophoresis were used to characterize a set of 75 clinicalLegionella pneumophila serogroup 1 isolates, with no apparent epidemiological link, obtained from 24 hospitals in Paris, France, from 1987 to 1997. Unexpectedly, 25 clinical isolates from 15 hospitals had an identical profile (termed type A) by both methods. The same profile was subsequently found in 16 of 64 randomly selected environmental L. pneumophila serogroup 1 isolates from 15 different sites in the Paris area. There was no evidence of geographic clustering or a peak incidence of type A isolation. Type A has not been found in France outside the Paris area, suggesting that a particular type of L. pneumophila serogroup 1 is specifically present in the Paris water distribution network.