Goldmann Oliver, Beineke Andreas, Medina Eva
Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig.
Department of Pathology, University of Veterinary Medicine Hannover, Germany.
J Infect Dis. 2017 Dec 12;216(11):1444-1451. doi: 10.1093/infdis/jix494.
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.
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。