Resistance to Reinfection in Experimental Histoplasmosis

Abstract

Mice previously infected with H. capsulatum are more resistant to a lethal challenge than normal mice of the same age and sex. This resistance is manifest by a decrease in death rate, the time of death in the previously infected and normal animals being the same. Apparently, neither the size of the sublethal infection nor the route of administration was of great importance in the induction of resistance, since mice injected intraperitoneally, intracerebrally, intravenously, or subcutaneously all showed resistance to lethal intracerebral challenge. In mice that were inoculated intraperitoneally with 10⁶ cells, it required about 72 hours for the resistance to become apparent. This increased resistance to challenge with H. capsulatum was not apparent when the animals were infected intraperitoneally with 10⁶ cells of B. dermatitidis, or C. albicans. Also, mice infected intraperitoneally with 10⁶ cells of H. capsulatum did not indicate any increased resistance to lethal intracerebral infection with C. albicans or B. dermatitidis. The antigen associated with virulence or protection seems to have a greater specificity than the antigens associated with precipitation or fixation (in the presence of complement) of antibody (4). In mice that developed resistance after a sublethal intraperitoneal inoculation, subsequent infection resulted in the greatest number of fungus cells developing in the spleen, liver, and usually the site of injection. This observation could be readily made on tissues of mice that had been challenged with a lethal dose of organisms. In intracerebrally challenged mice, the greatest number of fungus cells occurred in the liver, spleen, and brain; in the intraperitoneally challenged mice, the greatest number developed in the liver and spleen. It was also in these heavily infected tissues where marked reduction of fungus cells occurred, as compared to the numbers in the corresponding tissues of the control animals. In the control animals that had been intracerebrally challenged, the lungs and kidney had moderate numbers of H. capsulatum, previous infection caused little decrease in these tissues. The kidney and lung behaved similarly in the intraperitoneally challenged mice. However, the brains of the latter control group showed relatively low titers, with the previously infected mice showing increased resistance. In mice that had been challenged intranasally with a sublethal dose, the lungs of the control animals had by far the highest numbers of H. capsulatum. The resistant animals showed markedly lower numbers in the lungs. In general, therefore, previous infection tended to inhibit the growth of the fungus in the spleen, liver, and the site of inoculation, such as the brain or lungs. In the spleens of the control mice and guinea pigs, the numbers of fungus cells increased for the first 2 to 3 weeks (at dose levels used) after injection, and then gradually decreased. In the reinfected animals, however, the fungus did not multiply or develop to the extent that it did in the control animals. The titers of fungus cells remained at about the same low level in the spleen during the 8 post challenge weeks of observation.