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

小鼠抗恙虫病东方体感染的宿主防御机制分析

基本信息

批准号：
08670323
负责人：
TAMURA Akira
金额：
$ 1.41万
依托单位：
Niigata College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

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.

恙虫病的病原体东方恙虫病含有多种血清型和基因型变异，不同菌株对小鼠的致病性存在差异。本研究的第一部分通过免疫荧光试验和PCR-RFLP方法对日本和台湾获得的44个分离株进行了血清学和遗传特性分析。结果表明，日本分离株34株，分为4个型12个亚型，其他型3株。在测试中，台湾的所有 10 株菌株均与日本的菌株区分开来。这些结果表明恙虫病0. 中存在如此多的分化。我们还发现这些类型或亚型与对小鼠的毒力之间存在相关性。在本研究的后半部分，我们观察了注射后腹腔细胞中强毒株和无毒株的生长情况，发现强毒株可以在小鼠腹腔内巨噬细胞中繁殖，而无毒株则不能。这些强毒株和无毒株之间生长的差异也体现在对渗出巨噬细胞培养物的感染中。因此，我们分析了感染培养物中TNF-α、IL-1α和NO的产生，发现强毒株感染时不产生TNF，但无毒株感染时在感染早期短暂产生TNF。此外，向培养物中添加抗TNF抗血清导致无毒株的生长部分恢复，并且添加TNF抑制了强毒株的生长。从这些结果我们得出结论，强毒株抑制TNF产生和无毒株TNF产生增强导致巨噬细胞生长能力的差异，这与这些菌株的致病性差异相关。