Role of macrophages in innate and acquired host resistance to experimental scrub typhus infection of inbred mice.

Mechanisms of innate resistance to infection with the Gilliam strain of Rickettsia tsutsugamushi were examined using congenic strains of mice resistant (C3H/RV) or susceptible (C3H/He) to intraperitoneal infection. Both strains of mice were resistant to infection with 1,000 50% mouse lethal doses of rickettsiae if given intravenously. In both systems rickettsial replication occurred after intravenous infection, as evidenced by an increase in rickettsial numbers in the spleens of infected animals, followed by a decrease in rickettsiae to low levels by day 14 postinfection. Administration of the antimacrophage agents silica and carrageenan to C3H/He mice intravenously rendered these animals susceptible to lethal infection. Neither irradiation nor silica given individually rendered C3H/RV mice susceptible to intravenous infection. However, if silica and irradiation were given together, a lethal infection occurred after intravenous infection. C3H/RV mice became susceptible to lethal infection after sublethal doses of irradiation only if they were infected intraperitoneally. Administration of silica or carrageenan had no effect on the outcome of intraperitoneal infection of these mice with Gilliam rickettsiae. These data suggest that both strains of mice share innate resistance mechanisms to intravenous infection that consist of fixed macrophages. Resistance of C3H/RV mice to intraperitoneal infection, in contrast, apparently was dependent only on an irradiation-sensitive process

Host defenses in experimental scrub typhus: inflammatory response of congenic C3H mice differing at the Ric gene.

Two strains of C3H mice differed in their susceptibility to lethal infection with Rickettsia tsutsugamushi strain Gilliam. Adult C3H/RV mice were markedly more resistant to lethal infection than C3H/HeDub mice, and both were histocompatible as assessed by mixed-lymphocyte cultures and graft-versus-host responses. The inflammatory response of susceptible C3H/HeDub mice to intraperitoneal infection was evident approximately 5 days postinfection, and the magnitude of the cellular influx increased until death of the animal. The inflammation consisted of an early polymorphonuclear leukocyte response, followed by a mononuclear cell influx which persisted until death of the animal. The C3H/RV mice evidenced similar kinetics of cell influx, but the inflammatory response was significantly reduced in magnitude, and the response of C3H/RV animals to Gilliam was predominantly mononuclear in nature, with little influx of polymorphonuclear leukocytes into the peritoneal cavity. C3H/RV mice were rendered susceptible to Gilliam infection by induction of a nonspecific inflammation with thioglycolate if given 3 days after infection. Conversely, treatment of C3H/HeDub mice with indomethacin, an anti-inflammatory agent, prolonged survival after infection with Gilliam. The results of this study indicate that genetic resistance to Gilliam is not due simply to a greater host response to infection or, conversely, that susceptibility is due to a host response quantitatively lacking in a cellular component necessary for antirickettsial immunity