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Salmonella spp. are regarded as facultative intracellular bacterial pathogens which are found inside macrophages (Mphi) after i. v. infection. It is generally assumed that Mphi restrict the replication of the bacteria during infection. In this study we examined the in vivo activities of Mphi during experimental S. typhimurium infections, using a selective liposome-based Mphi elimination technique. Unexpectedly, elimination of Mphi prior to infection with virulent S. typhimurium decreased morbidity and mortality, suggesting that Mphi mediate the pathology caused by S. typhimurium. Removal of Mphi) during vaccination with attenuated S. typhimurium did not affect protection against challenge with virulent S. typhimurium, suggesting that Mphi are not required for the induction of protective immunity and that other cells must function as antigen-presenting cell to elicit T cell-mediated protection. However, Mphi appeared to be important effectors of protection against challenge infection since elimination of Mphi from vaccinated mice prior to challenge infection with virulent S. typhimurium significantly decreased protection. These results enhance our understanding of the control of S. typhimurium growth in vivo, and moreover suggest that Mphi play a major role in the pathology of virulent S. typhimurium infections. As such, these cells may present a novel target for therapeutic intervention.

Original publication

DOI

10.1002/1521-4141(200003)30:3<944::AID-IMMU944>3.0.CO;2-1

Type

Journal article

Journal

Eur J Immunol

Publication Date

03/2000

Volume

30

Pages

944 - 953

Keywords

Animals, Antibodies, Bacterial, Bacterial Vaccines, Clodronic Acid, Colony Count, Microbial, Female, Liposomes, Lymphocyte Activation, Macrophages, Mice, Mice, Inbred BALB C, Salmonella Infections, Animal, Salmonella typhimurium, T-Lymphocytes, Virulence