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

Salmonella sop. are regarded as facultative intracellular bacterial pathoge ns which are Sound inside macrophages (M Phi) after i.v. infection. It is g enerally assumed that M Phi, restrict the replication of the bacteria durin g infection. In this study we examined the in vivo activities of M Phi, dur ing experimental S. typhimurium infections, using a selective liposome-base d M Phi, elimination technique. Unexpectedly, elimination of M Phi, prior t o infection with virulent S. typhimurium decreased morbidity and mortality, suggesting that M Phi, mediate the pathology caused by S. typhimurium. Rem oval of M Phi during vaccination with attenuated S. typhimurium did not aff ect protection against challenge with virulent S. typhimurium, suggesting t hat M Phi are not required for the induction of protective immunity and tha t other cells must function as antigen-presenting cell to elicit T cell-med iated protection. However, M Phi appeared to be important effecters of prot ection against challenge infection since elimination of M Phi, from vaccina ted mice prior to challenge infection with virulent S. typhimurium signific antly decreased protection. These results enhance our understanding of the control of S. typhimurium growth in vivo, and moreover suggest that M Phi, play a major role in the pathology of virulent S. typhimurium infections. A s such, these cells may present a novel target for therapeutic intervention .