Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages

Salmonella serovars are associated with human diseases that range from mild gastroenteritis to host-disseminated enteric fever. Human infections by Sa lmonella enterica serovar Typhi can lead to typhoid fever, but this serovar does not typically cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, which ar e usually linked to localized gastroenteritis in humans and some animal spe cies, elicit a systemic infection in mice. To better understand these obser vations, multiple strains of each of several chosen serovars of Salmonella were tested for the ability in the nonopsonized state to enter, survive. an d replicate within human macrophage cells (U937 and elutriated primary cell s) compared with murine macrophage cells (J774A.1 and primary peritoneal ce lls); in addition, death of the infected macrophages was monitored. The ser ovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and murine peritoneal macrophages, compared with the significant, alm ost 100-fold declines in viable counts noted for serovar Typhi strains. Via ble counts for serovar Enteritidis either matched the level of serovar Typh ia (J774A.1 macrophages) or were comparable to counts for serovar Typhimuri um (murine peritoneal macrophages), Apoptosis was significantly higher in J 774A.1 cells infected with serovar Typhimurium strain LT2 compared to serov ar Typhi strain Ty2, On the other hand, serovar Typhi survived at a level u p to 100-fold higher in elutriated human macrophages and 2- to 3-fold highe r in U937 cells compared to the serovar Typhimurium and Enteritidis strains tested, Despite the differential multiplication of serovar Typhi during in fection of U937 cells, serovar Typhi caused significantly less apoptosis th an infections with serovar Typhimurium. These observations indicate variabi lity in intramacrophage survival and host cytotoxicity among the various se rovars and are the first to show differences in the apoptotic response of d istinct Salmonella serovars residing in human macrophage cells. These studi es suggest that nonopsonized serovar Typhimurium enters, multiplies within, and causes considerable, acute death of macrophages, leading to a highly v irulent infection in mice (resulting in death within 14 days). In striking contrast, nonopsonized serovar Typhi survives silently and chronically with in human macrophages, causing little cell death, which allows for intrahost dissemination and typhoid fever (low host mortality). The type of disease associated with any particular serovar of Salmonella is linked to the abili ty of that serovar both to persist within and to elicit damage in a specifi c host's macrophage cells.