Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.
Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.
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巨噬细胞是小鼠对非致死性巴贝虫感染的抵抗力和结果的决定因素。
DOI：
10.1128/iai.02128-14
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Xuan X.
中科院分区：
文献类型：
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作者：
Terkawi MA;Cao S;Herbas MS;Nishimura M;Li Y;Moumouni PF;Pyarokhil AH;Kondoh D;Kitamura N;Nishikawa Y;Kato K;Yokoyama N;Zhou J;Suzuki H;Igarashi I;Xuan X.
在本研究中，我们研究了巨噬细胞在BALB/c小鼠感染微小巴贝斯虫(人和啮齿动物巴贝斯虫病的病原体)结果中的作用。在小鼠感染微小芽孢杆菌的过程中，不同时间给予氯屈膦酸盐脂质体，以耗尽巨噬细胞。值得注意的是，宿主巨噬细胞在感染的早期和急性阶段的耗尽导致与小鼠显著死亡相关的寄生虫血症的显著增加。在感染的解决期和潜伏期，巨噬细胞的耗尽导致小鼠寄生虫血症的即时和短暂的恶化，并伴随着死亡。与单独接受药物治疗的小鼠相比，在感染急性期用幼小鼠的巨噬细胞重组氯屈膦脂质体治疗的小鼠，寄生虫血症略有减少，存活率提高。这些结果表明，巨噬细胞在控制和抵抗小鼠微小球虫感染中起着关键作用。此外，对宿主免疫反应的分析显示，巨噬细胞耗尽的小鼠减少了Th1细胞细胞因子的产生，包括干扰素(干扰素-γ)和肿瘤坏死因子-α(肿瘤坏死因子-α)。此外，不同时间巨噬细胞的耗尽夸大了干扰素-γ−/−缺陷小鼠和严重联合免疫缺陷小鼠感染的发病机制。总之，我们的数据为巨噬细胞在微小芽孢杆菌的抵抗和控制中的作用提供了重要的线索，并暗示免疫低下患者感染的严重性可能是由于巨噬细胞功能受损所致。
In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ−/−and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.