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慢性葡萄球菌感染期间类似于未成熟嗜酸性粒细胞的新型髓源性抑制细胞亚群的鉴定

Identification of a Novel Subset of Myeloid-Derived Suppressor Cells During Chronic Staphylococcal Infection That Resembles Immature Eosinophils.

作者信息

Goldmann Oliver, Beineke Andreas, Medina Eva

机构信息

Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig.

Department of Pathology, University of Veterinary Medicine Hannover, Germany.

出版信息

J Infect Dis. 2017 Dec 12;216(11):1444-1451. doi: 10.1093/infdis/jix494.

DOI:10.1093/infdis/jix494
PMID:29029332
Abstract

We have previously reported that myeloid-derived suppressor cells (MDSC), which are a heterogeneous population of immunosuppressive immature myeloid cells, expanded during chronic Staphylococcus aureus infection and promoted bacterial persistence by inhibiting effector T cells. Two major MDSC subsets, including monocytic MDSC and granulocytic MDSC, have been described to date. Here, we identified a new subset of MDSC (Eo-MDSC) in S. aureus-infected mice that phenotypically resembles eosinophils. Eo-MDSC exhibit eosinophilic cytoplasmic granules and express CD11b, the eosinophil marker Syglec-F, variable levels of CCR3, and low levels of interleukin-5Rα. Furthermore, Eo-MDSC accumulated at the site of infection and exerted a potent immunosuppressive effect on T-cell responses that was mediated by nitric oxide-dependent depletion of l-arginine. Increases in the number of Eo-MDSC by adoptive transfer caused a significant exacerbation of infection in S. aureus-infected mice. This study sheds new light on the heterogeneity and complexity of MDSC during chronic infection.

摘要

我们之前报道过,髓系来源的抑制性细胞(MDSC)是一群异质性的免疫抑制性未成熟髓样细胞,在慢性金黄色葡萄球菌感染期间会扩增,并通过抑制效应T细胞促进细菌持续存在。迄今为止,已描述了两个主要的MDSC亚群,包括单核细胞样MDSC和粒细胞样MDSC。在此,我们在感染金黄色葡萄球菌的小鼠中鉴定出一种新的MDSC亚群(嗜酸性粒细胞样MDSC,Eo-MDSC),其表型类似于嗜酸性粒细胞。Eo-MDSC表现出嗜酸性细胞质颗粒,并表达CD11b、嗜酸性粒细胞标志物Siglec-F、不同水平的CCR3以及低水平的白细胞介素-5Rα。此外,Eo-MDSC在感染部位积聚,并对T细胞反应发挥强大的免疫抑制作用,这种作用由一氧化氮依赖的L-精氨酸消耗介导。通过过继转移增加Eo-MDSC的数量会导致感染金黄色葡萄球菌的小鼠感染显著加剧。这项研究为慢性感染期间MDSC的异质性和复杂性提供了新的见解。

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