Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani
Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani
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DOI：
10.1128/iai.01388-07
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Tacchini-Cottier, Fabienne
中科院分区：
文献类型：
--
作者：
McFarlane, Emma;Perez, Cynthia;Tacchini-Cottier, Fabienne
中性粒细胞是炎症反应的关键组成部分，因此有助于杀死微生物。此外，最近的证据表明它们参与了免疫反应的发展。中性粒细胞在感染多诺瓦利什曼原虫后的第一周内的作用在本研究中进行了调查。当用NIMP-R14单克隆抗体选择性地清除多诺瓦尼L. donovani感染小鼠的中性粒细胞时，观察到脾脏和骨髓中的寄生虫数量显著增加，肝脏中的寄生虫数量较少。易感性增加与脾肿大增强、肝肉芽肿成熟延迟以及肉芽肿内诱导型一氧化氮合酶表达减少有关。在脾脏中，中性粒细胞耗竭与白细胞介素4（IL-4）和IL-10水平的显著升高以及CD4（+）和CD8(+) T细胞分泌γ干扰素的减少有关。与IgG2a相比，血清IL-4和IL-10的产生增加，利什曼特异性免疫球蛋白G1 （IgG1）的水平更高，表明中性粒细胞缺失小鼠优先诱导Th2反应。综上所述，这些数据表明中性粒细胞在针对多诺瓦氏杆菌的早期保护性反应中发挥了关键作用，无论是作为参与杀死寄生虫的效应细胞，还是作为影响保护性Th1免疫反应发展的重要参与者。
Neutrophils are key components of the inflammatory response and as such contribute to the killing of microorganisms. In addition, recent evidence suggests their involvement in the development of the immune response. The role of neutrophils during the first weeks post-infection with Leishmania donovani was investigated in this study. When L. donovani-infected mice were selectively depleted of neutrophils with the NIMP-R14 monoclonal antibody, a significant increase in parasite numbers was observed in the spleen and bone marrow and to a lesser extent in the liver. Increased susceptibility was associated with enhanced splenomegally, a delay in the maturation of hepatic granulomas, and a decrease in inducible nitric oxide synthase expression within granulomas. In the spleen, neutrophil depletion was associated with a significant increase in interleukin 4 (IL-4) and IL-10 levels and reduced gamma interferon secretion by CD4(+) and CD8(+) T cells. Increased production of serum IL-4 and IL-10 and higher levels of Leishmania-specific immunoglobulin G1 (IgG1) versus IgG2a revealed the preferential induction of Th2 responses in neutrophil-depleted mice. Altogether, these data suggest a critical role for neutrophils in the early protective response against L. donovani, both as effector cells involved in the killing of the parasites and as significant players influencing the development of a protective Th1 immune response.