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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OBJECTIVE: To delineate, using two different typing systems, the clonal relatedness of 40 isolates of extended-spectrum beta-lactamase (ESbetaIa)-producing Proteus mirabilis obtained over a period of 7 years in six hospitals in the Paris area and two in Pas-de-Calais. METHODS: Random amplified polymorphic DNA (RAPD) polymerase chain reaction typing was applied by using three random primers on the ESbetaIa-producing P. mirabilis isolates and on isogenic Escherichia coli strains with or without plasmids encoding the representative resistance pattern transferred from P. mirabilis. Quantitative antibiogram typing, which was also applied to the P. mirabilis isolates, was used to define the euclidean distance between these strains. RESULTS: After having demonstrated that P. mirabilis plasmids did not influence chromosomal DNA amplification, we could classify the ESbetaIa-producing P. mirabilis isolates into 12 groups based on RAPD fingerprints. The same isolates were classified into 19 groups by quantitative antibiogram typing. Despite this difference in group numbers, general concordance between the typing systems was observed. This allowed us to show that the greater number of isolates in some hospitals belonged to a single strain and that single isolates obtained in different hospitals generally represented unique strains. CONCLUSIONS: A small number of ESbetaIa-producing P. mirabilis strains was isolated during 7 years in the eight medical centers studied, and the number of different strains identified suggested that inter-hospital transfer had not occurred.