Molecular immunological analysis of early resistance existed in susceptible mice to protozoan infection.

分子免疫学分析表明易感小鼠对原虫感染存在早期抵抗力。

• 批准号: 11470064
• 负责人: SENDO Fujiro
• 金额: $ 8.96万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470064/
• 关键词: protozoan infection; early stage resistance; neutrophil; BALB; c mouse; Leishmania major; cytokine; mRNA; Trypanosoma cruzi; Leishmania major; neutrophil; cytokine; 感受性マウス; 好中球枯渇; 虫血症

To understand the immunomodulatory roles of neutrophils in Leishmania major infection, we examined-the expression of cytokine and/or chemokine mRNAs from neutrophils of the infected resistant C3H/HeJ and susceptible BALB/c mice. We also examined the effects of neutrophil depletion on the expression of cytokine mRNAs by peritoneal macrophages and draining lymph nodes cells and on the footpad lesions and parasite burdens in these mice. Neutrophils from resistant C3H/HeJ but not from susceptible BALB/c mice expressed mRNAs for IL-12p40, IFN-1γ, TNF-α, and a Th1 cell chemoattractive chemokine, monikine induced by IFN-γ (MIG). Neutrophil depletion of the resistant mice reduced the expression of IFN-γ and TNF-α mRNAs in peritoneal macrophages, but did not affected the expression of IL-12p40 mRNAs in draining lymph nodes and the growth of footpad lesions. On the other hand, neutrophil depletion of susceptible BALB/c mice did not affect the expression of TNF-α and a Th2 cell chemoattractive chemokine, monocyte derived chemokine (MDC) in peritoneal macrophages, but induced the early stage expression of IL-4 mRNA in draining lymph nodes cells and exacerbated the footpad lesions and increased the parasite burden. Our results suggest that even in susceptible BALB/c but not in C3H/HeJ mice there is a certain resistance requiring neutrophils at the early stage of infection.

为了了解中性粒细胞在利什曼原虫感染中的免疫调节作用，我们检测了感染的耐药C3 H/HeJ和易感BALB/c小鼠的中性粒细胞的细胞因子和/或趋化因子mRNA的表达。我们还研究了中性粒细胞耗竭对腹膜巨噬细胞和引流淋巴结细胞的细胞因子mRNA表达的影响，以及对这些小鼠的足垫病变和寄生虫负荷的影响。来自耐药C3 H/HeJ但不来自易感BALB/c小鼠的中性粒细胞表达IL-12 p40、IFN-1γ、TNF-α和IFN-γ诱导的Th 1细胞趋化因子monikine的mRNA。耐药小鼠的中性粒细胞耗竭降低了腹腔巨噬细胞中IFN-γ和TNF-α mRNA的表达，但不影响引流淋巴结中IL-12 p40 mRNA的表达和足垫病变的生长。另一方面，易感BALB/c小鼠的中性粒细胞耗竭不影响腹腔巨噬细胞中TNF-α和Th 2细胞趋化因子单核细胞衍生趋化因子（MDC）的表达，但诱导引流淋巴结细胞中IL-4 mRNA的早期表达，加重足垫病变，增加寄生虫负荷。我们的研究结果表明，即使在敏感的BALB/c，但不是在C3 H/HeJ小鼠有一定的阻力，需要中性粒细胞在感染的早期阶段。