Host-parasite interactions with peritoneal macrophages of mice and rats in vitro and in vivo

Abstract

This paper deals with the intracellular multiplication of mycobacteria in peritoneal macrophages from mice and rats immunized with tubercle bacilli or pretreated with Triton WR 1339. If unstimulated macrophages were used, almost unrestricted multiplication of mycobacteria was observed in macrophages from both vaccinated and pretreated hosts after infection of the cells in vitro. Only when the infection of the cells was perfored in the peritoneal cavity of vaccinated hosts did the macrophages display a high degree of inhibition. This striking difference in the behavior of macrophages infected in vitro and in vivo is explained by the local inflammation caused by the intraperitoneal infection, which leads to an influx of T-cell mediators. When macrophages from hosts pretreated with Triton WR 1339 were used, inhibition of the multiplication of mycobacteria within cells infected in vitro or in vivo was very slight, though this compound displayed a marked protective effect in the host. Addition of streptomycin to the culture medium caused a strong inhibition of intracellular mycobacteria even in small concentrations; there was no difference between normal and "immune" macrophages. When rats were infected with virulent tubercle bacilli, they were initially fully susceptible to the infection but showed rapid onset of a strong immune response.

Mycobacterium tuberculosis Dissemination Plays a Critical Role in Pathogenesis

“…The "trojan horse" theory of dissemination hypothesized that M. tuberculosis traffics within alveolar macrophages (AM) across the airway epithelium. This is an attractive theory, because it is well-established that AMs are one of the first and most numerous types cells to become infected with tuberculosis in both humans and animal models (Berthrong, 1970;Wagner, 1975;Srivastava et al, 2014). M. tuberculosis can survive and replicate within AMs, and the ability of this cell type to cross into and out of the circulatory and lymphatic systems is wellcharacterized.…”

WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop inMycobacterium marinum

“…equivalent (37)(38)(39). In the host, pathogenic mycobacteria are taken up by professional phagocytes, including macrophages (40,41). The ESX-1 system damages the phagosomal membrane, allowing bacterial interaction with the cytosol and survival.…”