Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Parasite Immunol. 2014 Jan;36(1):13-31. doi: 10.1111/pim.12078.
Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.
中性粒细胞参与了对病原体的免疫反应的早期阶段。在这里,我们研究了中性粒细胞在感染 Leishmania amazonensis 的 BALB/c 和 C57BL/6 小鼠中的作用。首先,我们发现在感染后 6 至 24 小时之间中性粒细胞的积累,然后在 72 小时后中性粒细胞数量减少。接下来,我们使用 RB6-8C5 或 1A8 mAb 在感染前耗尽中性粒细胞。在 BALB/c 小鼠中,中性粒细胞耗竭导致病变发展更快,寄生虫数量增加,并且在感染的第一周内精氨酸酶活性更高,但在 C57BL/6 小鼠中则不然。易感性增加伴随着抗 L. amazonensis IgG 水平的升高以及 IL-10 和 IL-17 的产生增加。因为 IL-10 是对 Leishmania 感染易感性的介质,所以我们使用抗 IL-10R 阻断中性粒细胞耗竭小鼠中的 IL-10 信号。有趣的是,抑制 IL-10 信号阻断了在中性粒细胞耗竭小鼠中观察到的寄生虫负荷增加,表明寄生虫增殖至少部分是由 IL-10 介导的。此外,我们测试了 IL-17 在炎症性巨噬细胞中的作用,并观察到 IL-17 增加了精氨酸酶活性并有利于寄生虫生长。综上所述,我们的数据表明中性粒细胞控制寄生虫数量并限制 BALB/c 小鼠感染的第一周内病变的发展。