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

恙虫病东方体是恙虫病的病原体之一，其血清型和基因型多样，对小鼠的致病性也存在差异。本研究的第一部分采用免疫荧光试验和PCR-RFLP方法对日本和台湾地区分离的44株恙虫病东方体进行了血清学和遗传学特性分析。结果表明，日本分离的34株菌可分为4个类型，其中12个亚型，其它类型3株。台湾的10个分离株与日本的分离株在试验中均能区分。这些结果表明，在0。恙虫病。本研究的后半部分，我们观察了强毒株和无毒毒株在小鼠腹腔巨噬细胞内的生长情况，发现强毒株能在小鼠腹腔巨噬细胞内增殖，而无毒毒株不能。因此，我们分析了感染培养物中TNF-α、IL-1 α和NO的产生，发现强毒株感染不产生TNF，但在无毒毒株感染中观察到在感染早期TNF的暂时产生。此外，加入TNF抗血清后，弱毒株的生长部分恢复，而加入TNF则抑制了强毒株的生长。从这些结果可以看出，强毒株抑制TNF产生和弱毒株增强TNF产生是导致巨噬细胞生长能力差异的原因。这与菌株致病性的差异有关。

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.