The circadian clock in immune cells controls the magnitude of Leishmania parasite infection.
The circadian clock in immune cells controls the magnitude of Leishmania parasite infection.
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DOI：
10.1038/s41598-017-11297-8
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发表时间：
2017-09-07
影响因子：
4.6
通讯作者：
Cermakian N
中科院分区：
文献类型：
--
作者：
Kiessling S;Dubeau-Laramée G;Ohm H;Labrecque N;Olivier M;Cermakian N
细胞内寄生虫利什曼原虫在感染时使用中性粒细胞和巨噬细胞作为宿主细胞。这些免疫细胞拥有自己的内在生物钟，已知会影响其功能的许多方面。因此，我们测试了宿主生物钟是否调节小鼠利什曼原虫感染的程度。在体外和足垫和腹腔感染两种不同的体内模型中，骨髓源性巨噬细胞的寄生感染程度在24小时内发生变化。在体内，这与嗜中性粒细胞和巨噬细胞浸润到感染部位的时间依赖性和节律性趋化因子的表达是平行的。因此，在体内观察到的节律性寄生虫感染可能是由趋化剂的昼夜表达和随后的中性粒细胞和巨噬细胞的节律性浸润引发的。重要的是，在缺乏生物钟的巨噬细胞中，当免疫细胞中缺乏生物钟的小鼠被感染时，所有的节律都被废除了。因此，我们证明了免疫细胞中生物钟在调节利什曼原虫感染程度方面的关键作用。据我们所知，这是第一份显示生物钟控制哺乳动物原生寄生虫感染的报告。了解宿主-寄生虫相互作用的定时调节将有助于开发更好的预防和治疗策略来对抗媒介传播的疾病。
The intracellular parasite Leishmania uses neutrophils and macrophages as host cells upon infection. These immune cells harbour their own intrinsic circadian clocks, known to influence many aspects of their functions. Therefore, we tested whether the host circadian clocks regulate the magnitude of Leishmania major infection in mice. The extent of parasitic infection varied over 24 h in bone marrow-derived macrophages in vitro and in two different in vivo models, footpad and peritoneal cavity infection. In vivo this was paralleled by time of day-dependent neutrophil and macrophage infiltration to the infection site and rhythmic chemokine expression. Thus, rhythmic parasitic infection observed in vivo was likely initiated by the circadian expression of chemoattractants and the subsequent rhythmic infiltration of neutrophils and macrophages. Importantly, all rhythms were abolished in clock-deficient macrophages and when mice lacking the circadian clock in immune cells were infected. Therefore we demonstrated a critical role for the circadian clocks in immune cells in modulating the magnitude of Leishmania infection. To our knowledge this is the first report showing that the circadian clock controls infection by protozoan parasites in mammals. Understanding the timed regulation of host-parasite interactions will allow developing better prophylactic and therapeutic strategies to fight off vector-borne diseases.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.6
作者：
Losada-Barragán M;Umaña-Pérez A;Cuervo-Escobar S;Berbert LR;Porrozzi R;Morgado FN;Mendes-da-Cruz DA;Savino W;Sánchez-Gómez M;Cuervo P
通讯作者：
Cuervo P
影响因子：
3.1
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通讯作者：
McDowell, Mary Ann
影响因子：
10.3
作者：
Laranjeira-Silva, Maria Fernanda;Zampieri, Ricardo A.;Markus, Regina P.
通讯作者：
Markus, Regina P.
影响因子：
3.5
作者：
Meireles, ACA;Rivas, GBD;Peixoto, AA
通讯作者：
Peixoto, AA