Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice

Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice
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小鼠利什曼原虫感染早期的趋化因子、自然杀伤细胞和粒细胞

DOI:
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发表时间:
2001
期刊:
Medical Microbiology and Immmunology
影响因子:
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通讯作者:
T. Laskay
T. Laskay
中科院分区:
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文献类型:
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作者:
K. Müller;G. Zandbergen;B. Hansen;H. Laufs;Nicole Jahnke;W. Solbach;T. Laskay

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抽象的。在本研究中,白细胞进入感染的皮肤和引流淋巴结(LN)的早期招聘进行了研究皮下感染利什曼原虫主要前鞭毛体小鼠后。从感染皮肤中回收的细胞的流式细胞术分析显示,GR-1+粒细胞早在感染后10小时就存在,因此代表了第一个被招募到感染部位的白细胞群。粒细胞的迁移与感染皮肤中嗜中性粒细胞趋化因子KC的快速mRNA表达相关。此外,L.发现主要的前鞭毛体在体外产生对人嗜中性粒细胞具有趋化性的因子。用人类中性粒细胞进行的实验表明,这些细胞能够吞噬寄生虫。感染后24 h,感染部位出现自然杀伤(NK)细胞。研究发现,耐药小鼠中NK细胞的迁移与NK细胞活化趋化因子IP-10的表达相关。用重组小鼠IP-10治疗敏感的BALB/c小鼠导致引流LN中NK细胞的细胞毒活性显著增加。这些数据表明,无论是早期的趋化因子基因的表达和生产的趋化因子的寄生虫本身调节定点迁移和激活的先天性免疫反应的细胞,并建议的作用,趋化因子的早期防御寄生虫。
Abstract. In the present study the early recruitment of leukocytes into the infected skin and into the draining lymph node (LN) was investigated after subcutaneous infection of mice with Leishmania major promastigotes. Flow cytometric analysis of cells recovered from the infected skin revealed that GR-1+ granulocytes were present as early as 10 h after infection, thus representing the first leukocyte population to be recruited to the site of infection. The migration of granulocytes was shown to be associated with a rapid mRNA expression of the neutrophil-attracting chemokine KC in the infected skin. Moreover, L. major promastigotes were found to produce factor(s) that are chemotactic for human neutrophils in vitro. Experiments with human neutrophils revealed that these cells are able to phagocytose the parasites. Natural killer (NK) cells appeared at the site of infection 24 h after infection. The migration of NK cells in resistant mice was found to correlate with the expression of the NK cell-activating chemokine IP-10. Treatment of susceptible BALB/c mice with recombinant mouse IP-10 resulted in a significantly increased NK cell cytotoxic activity in the draining LN. These data suggest that both the early chemokine gene expression and the production of chemotactic factors by the parasites themselves regulate the site-directed migration and activation of cells of the innate immune response, and suggest a role of chemotactic factors in the early defense against the parasites.