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A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.
Immunity ( IF 25.5 ) Pub Date : 2019-03-27 , DOI: 10.1016/j.immuni.2019.03.001
Baptiste Janela 1 , Amit A Patel 2 , Mai Chan Lau 3 , Chi Ching Goh 3 , Rasha Msallam 3 , Wan Ting Kong 3 , Michael Fehlings 3 , Sandra Hubert 3 , Josephine Lum 3 , Yannick Simoni 3 , Benoit Malleret 4 , Francesca Zolezzi 5 , Jinmiao Chen 3 , Michael Poidinger 3 , Ansuman T Satpathy 6 , Carlos Briseno 6 , Christian Wohn 7 , Bernard Malissen 8 , Kenneth M Murphy 6 , Alexander A Maini 2 , Leen Vanhoutte 9 , Martin Guilliams 10 , Emmanuel Vial 11 , Laurent Hennequin 11 , Evan Newell 3 , Lai Guan Ng 3 , Philippe Musette 12 , Simon Yona 2 , Feriel Hacini-Rachinel 11 , Florent Ginhoux 1
Affiliation  

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

中文翻译:


I 型传统树突状细胞的一个子集通过 VEGFα 介导的中性粒细胞募集来控制皮肤细菌感染。



皮肤常规树突状细胞 (cDC) 以两个不同的亚群存在,即 cDC1 和 cDC2,它们维持对病原体的免疫性以及对自身和微生物群的耐受性的平衡。在这里,我们研究了真皮 cDC1 和 cDC2 在细菌感染期间的作用,特别是痤疮丙酸杆菌 (P. acnes)。 cDC1(而非 cDC2)通过控制中性粒细胞向发炎部位的募集以及其中的存活和功能来调节小鼠真皮中对痤疮丙酸杆菌的免疫反应的强度。单细胞 mRNA 测序显示,这种调节依赖于一小部分激活的 EpCAM+CD59+Ly-6D+ cDC1 分泌细胞因子血管内皮生长因子 α (VEGF-α)。在金黄色葡萄球菌、卡介苗 (BCG) 或大肠杆菌感染期间以及在人类皮肤细菌损伤模型中也观察到真皮 cDC1 招募中性粒细胞。因此,皮肤 cDC1 是皮肤免疫先天反应的重要调节因子,其作用超出了经典抗原呈递的范围。
更新日期:2019-03-27
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