SALMONELLA STIMULATE MACROPHAGE MACROPINOCYTOSIS AND PERSIST WITHIN SPACIOUS PHAGOSOMES

Light microscopic studies of phagocytosis showed that Salmonella typhi murium entered mouse macrophages enclosed in spacious phagosomes (SP). Viewed by time-lapse video microscopy, bone marrow-derived macrophage s exposed to S. typhimurium displayed generalized plasma membrane ruff ling and macropinocytosis. Phagosomes containing Salmonella were morph ologically indistinguishable from macropinosomes. SP formation was obs erved after several methods of bacterial opsonization, although bacter ia opsonized with specific IgG appeared initially in small phagosomes that later enlarged. In contrast to macropinosomes induced by growth f actors, which shrink completely within 15 min, SP persisted in the cyt oplasm, enlarging often by fusion with macropinosomes or other SP. A S almonella strain containing a constitutive mutation in the phoP virule nce regulatory locus (PhoP(c)) induced significantly fewer SP. Similar to Yersinia enterocolitica, PhoP(c) bacteria entered macrophages in c lose-fitting phagosomes, consistent with that expected for conventiona l receptor-mediated phagocytosis. These results suggest that formation of SP contributes to Salmonella survival and virulence.