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 effectors 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.