National Heart and Lung Institute, Department of Inflammation, Development & Repair, Imperial College London, UK.
Manchester Collaborative Centre for Inflammation Research (MCCIR), Manchester, UK.
Eur J Immunol. 2019 Sep;49(9):1380-1390. doi: 10.1002/eji.201847861. Epub 2019 Aug 7.
CD200 receptor 1(CD200R1) signalling limits myeloid cell responses and reduces autoimmunity, alloimmunity and viral-mediated immunopathology, but has never been examined in the context of eosinophilic inflammation. Susceptibility to lung fungal infection is associated with T-helper 2 (Th2) cytokine dominated responses and strong eosinophilic pathology. Blockade of CD200R1 enhances type I cytokine responses in many infectious and non-infectious settings and so may promote a more protective response to fungal infection. By contrast, we demonstrate that, rather than promoting type I cytokine responses, CD200R1 blockade enhanced eosinophilia in a mouse model of Cryptococcus neoformans infection, whereas CD200R1 agonism reduced lung eosinophilia - with neither strategy completely altering fungal burden. Thus, we reveal a surprising disconnect between pulmonary eosinophilia and cryptococcal burden and dissemination. This research has 2 important implications. Firstly, a lack of CD200R1 signalling enhances immune responses regardless of cytokine polarisation, and secondly reducing eosinophils does not allow protective immunity to develop in susceptible fungal system. Therefore, agonists of CD200R1 may be beneficial for eosinophilic pathologies.
CD200 受体 1（CD200R1）信号限制了髓样细胞的反应，减少了自身免疫、同种免疫和病毒介导的免疫病理，但从未在嗜酸性炎症的背景下进行过研究。对肺部真菌感染的易感性与辅助性 T 细胞 2（Th2）细胞因子主导的反应和强烈的嗜酸性粒细胞病理学有关。在许多感染和非感染性环境中，阻断 CD200R1 增强了 I 型细胞因子的反应，因此可能促进对真菌感染的更具保护作用的反应。相比之下，我们证明，阻断 CD200R1 增强了隐球菌感染小鼠模型中的嗜酸性粒细胞增多，而 CD200R1 激动剂则减少了肺部嗜酸性粒细胞增多——这两种策略都没有完全改变真菌负荷。因此，我们揭示了肺部嗜酸性粒细胞增多和隐球菌负担和传播之间令人惊讶的脱节。这项研究有两个重要意义。首先，无论细胞因子极性如何，缺乏 CD200R1 信号都会增强免疫反应，其次，减少嗜酸性粒细胞并不能使易感真菌系统产生保护性免疫。因此，CD200R1 的激动剂可能对嗜酸性粒细胞病理有益。
