Behavior of Neutrophil Granulocytes during Toxoplasma gondii Infection in the Central Nervous System.
Behavior of Neutrophil Granulocytes during Toxoplasma gondii Infection in the Central Nervous System.
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DOI：
10.3389/fcimb.2017.00259
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发表时间：
2017
影响因子：
5.7
通讯作者：
Dunay IR
中科院分区：
文献类型：
--
作者：
Biswas A;French T;Düsedau HP;Mueller N;Riek-Burchardt M;Dudeck A;Bank U;Schüler T;Dunay IR
脑弓形虫病的特征在于脑驻留细胞的活化和特异性免疫细胞亚群从外周向中枢神经系统（CNS）的募集。我们的研究表明，快速侵入的Ly 6 G+中性粒细胞是干扰素-γ（IFN-γ）的早期非淋巴源，干扰素-γ是已知宿主对弓形虫（T.弓形虫）。在选择性消耗Ly 6 G+中性粒细胞后，我们检测到CNS中IFN-γ产生减少和寄生虫负荷增加。Ly 6 G+细胞的消融导致Ly 6Chi单核细胞进入CNS的募集减少，表明明显的相互作用。此外，我们确定浸润的Ly 6 G+中性粒细胞是一个异质性群体。Ly 6 G + CD 62-LhiCXCR 4+亚群释放cathelicidin-related antimicrobial peptide（CRAMP），其可促进单核细胞动力学。另一方面，Ly 6 G + CD 62-LloCXCR 4+亚群产生IFN-γ以建立早期炎症反应。总的来说，我们的研究结果表明，招募的Ly 6 G + CXCR 4+中性粒细胞在CNS中显示出异质性，在实验性脑弓形虫病的寄生虫控制和免疫调节中具有至关重要的效应子功能。
Cerebral toxoplasmosis is characterized by activation of brain resident cells and recruitment of specific immune cell subsets from the periphery to the central nervous system (CNS). Our studies revealed that the rapidly invaded Ly6G+ neutrophil granulocytes are an early non-lymphoid source of interferon-gamma (IFN-γ), the cytokine known to be the major mediator of host resistance to Toxoplasma gondii (T. gondii). Upon selective depletion of Ly6G+ neutrophils, we detected reduced IFN-γ production and increased parasite burden in the CNS. Ablation of Ly6G+ cells resulted in diminished recruitment of Ly6Chi monocytes into the CNS, indicating a pronounced interplay. Additionally, we identified infiltrated Ly6G+ neutrophils to be a heterogeneous population. The Ly6G+CD62-LhiCXCR4+ subset released cathelicidin-related antimicrobial peptide (CRAMP), which can promote monocyte dynamics. On the other hand, the Ly6G+CD62-LloCXCR4+ subset produced IFN-γ to establish early inflammatory response. Collectively, our findings revealed that the recruited Ly6G+CXCR4+ neutrophil granulocytes display a heterogeneity in the CNS with a repertoire of effector functions crucial in parasite control and immune regulation upon experimental cerebral toxoplasmosis.