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

Abstract

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.