Biswas Aindrila, French Timothy, Düsedau Henning P, Mueller Nancy, Riek-Burchardt Monika, Dudeck Anne, Bank Ute, Schüler Thomas, Dunay Ildiko Rita
Institute of Inflammation and Neurodegeneration, Otto-von-Guericke University MagdeburgMagdeburg, Germany.
Institute for Molecular and Clinical Immunology, Otto-von-Guericke University MagdeburgMagdeburg, Germany.
Front Cell Infect Microbiol. 2017 Jun 21;7:259. doi: 10.3389/fcimb.2017.00259. eCollection 2017.
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 (). 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 Ly6C monocytes into the CNS, indicating a pronounced interplay. Additionally, we identified infiltrated Ly6G neutrophils to be a heterogeneous population. The Ly6GCD62-LCXCR4 subset released cathelicidin-related antimicrobial peptide (CRAMP), which can promote monocyte dynamics. On the other hand, the Ly6GCD62-LCXCR4 subset produced IFN-γ to establish early inflammatory response. Collectively, our findings revealed that the recruited Ly6GCXCR4 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.
脑弓形虫病的特征是脑内固有细胞被激活，以及特定免疫细胞亚群从外周被募集到中枢神经系统（CNS）。我们的研究表明，迅速侵入的Ly6G中性粒细胞是干扰素-γ（IFN-γ）的早期非淋巴细胞来源，已知该细胞因子是宿主抵抗（此处原文括号内容缺失）的主要介质。在选择性清除Ly6G中性粒细胞后，我们检测到中枢神经系统中IFN-γ产生减少且寄生虫负荷增加。Ly6G细胞的消融导致Ly6C单核细胞向中枢神经系统的募集减少，表明存在明显的相互作用。此外，我们确定浸润的Ly6G中性粒细胞是一个异质性群体。Ly6G⁺CD62⁻CXCR4⁺亚群释放与抗菌肽相关的cathelicidin（CRAMP），其可促进单核细胞动态变化。另一方面，Ly6G⁻CD62⁺CXCR4⁻亚群产生IFN-γ以建立早期炎症反应。总体而言，我们的研究结果表明，在实验性脑弓形虫病中，募集的Ly6G⁺CXCR4⁺中性粒细胞在中枢神经系统中表现出异质性，具有在寄生虫控制和免疫调节中起关键作用的一系列效应功能。
