Resistance of Mice with Experimental Histoplasmosis to Infection with Rickettsia Typhi

Abstract

Discussion and Summary Evidence is presented that Histoplasma capsulatum exerted a striking modifying effect upon the course of infection with Rickettsia typhi in mice. This antagonistic action of one agent upon another apparently was not due to specific antibodies since immune serum from guinea pigs with experimental histoplasmosis failed to show any neutralizing effect in the mouse toxin neutralization test, or any fixation of complement in the presence of typhus antigen. Also antityphus guinea pig sera did not show complement-fixing, precipitating, or neutralizing antibodies against H. capsulatum (10). Of particular interest was the fact that the modifying effect occurred only when both agents were injected by the intraperitoneal route. Intravenous, intracerebral, or subcutaneous injection of either one or both agents resulted in slight, if any, inhibitory effect on the course of typhus infection. The necessity for administering both agents via the intraperitoneal route was also indicated in the experiments with R. typhi toxin. This importance of the inoculation route was also emphasized by Horsfall and McCarty (5) who noted that the modifying effect of a non-hemolytic streptococcus on the pneumonia virus of mice (PVM virus) occurred only when both agents were administered by the intranasal route. The time and dose relationships between H. capsulatum and R. typhi were of importance in demonstrating the inhibitory effect. Inhibition occurred only when the interval between injections was sufficient to permit propagation of the fungus to a necessary level. This interval could be shortened or lengthened according to the number of fungus cells in the initial injection. With doses of 109 cells of the fungus, maximum resistance occurred after a 2-day interval. Were doses of H. capsulatum higher than 109 employed, a blocking effect following simultaneous injection of the agents might have occurred. The modifying effect of H. capsulatum on R. typhi infections was not exhibited by six other fungi tested. On the other hand, H. capsulatum was capable of modifying infection not only by R. typhi but also by R. tsutsugamushi. Inhibition of typhus infection was not dependent on active growth of H. capsulatum, since a definite modifying action was produced by killed fungus cells. However, the latter effect was not as great as that following injection of living cells.