Dual role for macrophages in vivo in pathogenesis and control of murine Salmonella enterica var. Typhimurium infections

Salmonella spp. are regarded as facultative intracellular bacterial pathogens which are found inside macrophages (MΦ) after i.v. infection. It is generally assumed that MΦ restrict the replication of the bacteria during infection. In this study we examined the in vivo activities of MΦ during experimental S. typhimurium infections, using a selective liposome-based MΦ, elimination technique. Unexpectedly, elimination of MΦ prior to infection with virulent S. typhimurium decreased morbidity and mortality, suggesting that MΦ mediate the pathology caused by S. typhimurium. Removal of MΦ during vaccination with attenuated S. typhimurium did not affect protection against challenge with virulent S. typhimurium, suggesting that MΦ 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, MΦ appeared to be important effecters of protection against challenge infection since elimination of MΦ 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 MΦ play a major role in the pathology of virulent S. typhimurium infections. As such, these cells may present a novel target for therapeutic intervention.