Analyses of host-defense mechanism in mice against infection of Orientia tsutsugamushi

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Orientia tsutsugamushi, a causative agent of scrub typhus, contains various serotypic and genotypic variants, and difference of pathogenicity to mice is recognized among strains, In the first part of this study, serological and genetical properties of 44 isolates obtained in Japan and Taiwan were analyzed by immunofluorescence test and PCR-RFLP methods. The results indicated that 34 isolates in Japan were classified into 4 types containing 12 subtypes, and 3 strains of other types. All 10 isolates in Taiwan were distinguished from isolates in Japan in the tests. These results indicated the existence of so many divergence in 0. tsutsugamushi. Also we found that there is a relation between these types or subtypes and virulence to mice.In the latter part of this study, we observed growth of virulent and avirulent strains in intraperitoneal cells after injections, and found that virulent strain can multiply in intraperitoneal macrophage of mice but avirulent strain cannot These differences of growth between virulent and avirulent strains were also seen in infection to exuded macrophage cultures. Therefore we analyzed the production of TNF-alpha, IL-1alpha and NO in the infected culture and found that TNF was not produced by infection with virulent strains but a temporal production of TNF in the early stage of infection was seen in infection with avirulent strain. Furthermore, addition of anti-TNF antiserum to the culture resulted in the partial recovery of growth of avirulent strain, and addition of TNF suppressed the growth of virulent strain, From these results we conclude that suppression of TNF production with virulent strain and enhancement of TNF production with avirulent strain result in the difference of capability in growth in macrophage, and this correlates to the difference of pathogenicities of these strains.