Hammi Ikram, Giron-Michel Julien, Riyad Myriam, Akarid Khadija, Arnoult Damien
Health & Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca (UH2C), Casablanca, Morocco.
INSERM UMR-S-MD 1197, Ministère des Armées et Université Paris Saclay, Villejuif, France.
Parasit Vectors. 2024 Dec 18;17(1):517. doi: 10.1186/s13071-024-06593-y.
Leishmania is the causal parasite of leishmaniasis, a neglected tropical disease affecting millions of individuals worldwide, and its dissemination is linked to climate change. Despite the complexity and effectiveness of the immune response, the parasite has developed many strategies to evade it and take control of the host cell to replicate. These evasion strategies start at early stages of infection by hijacking immune receptors to mitigate the cellular response. In this study, we examined whether Leishmania uses the Fc receptor FcγRIIA/CD32a and its downstream signaling pathways to evade the host immune response.
Regarding in vivo studies, CD32a transgenic mice and the corresponding wild types were infected with Leishmania major Friedlin strain. For the in vitro experiments, BMDMs isolated from WT or CD32a transgenic mice and control or CD32a knockdown differentiated THP-1s were infected with two species of Leishmania, Leishmania major and L. tropica.
In vivo, expression of FcγRIIA/CD32a was found to accelerate the signs of inflammation while simultaneously preventing the formation of necrotic lesions after Leishmania infection. In infected macrophages, the presence of FcγRIIA/CD32a did not affect the secretion of proinflammatory cytokines, while the balance between ITAMa and ITAMi proteins was disturbed with improved Fyn and Lyn activation. Unexpectedly, infection with L. tropica but not L. major triggered an intracytoplasmic processing of FcγRIIA/CD32a.
Our observations underscore the significance of FcγRIIA/CD32a in cutaneous leishmaniasis and its potential use as a therapeutic target.
利什曼原虫是利什曼病的致病寄生虫，利什曼病是一种被忽视的热带疾病，影响着全球数百万人，其传播与气候变化有关。尽管免疫反应复杂且有效，但该寄生虫已发展出许多策略来逃避免疫反应并控制宿主细胞进行复制。这些逃避策略在感染早期就开始通过劫持免疫受体来减轻细胞反应。在本研究中，我们研究了利什曼原虫是否利用Fc受体FcγRIIA/CD32a及其下游信号通路来逃避宿主免疫反应。
在体内研究方面，用利什曼原虫弗里德林菌株感染CD32a转基因小鼠和相应的野生型小鼠。在体外实验中，用两种利什曼原虫，即大利什曼原虫和热带利什曼原虫感染从野生型或CD32a转基因小鼠分离的骨髓来源的巨噬细胞（BMDM）以及对照或CD32a基因敲低的分化的THP-1细胞。
在体内，发现FcγRIIA/CD32a的表达会加速炎症迹象，同时在利什曼原虫感染后防止坏死性病变的形成。在受感染的巨噬细胞中，FcγRIIA/CD32a的存在不影响促炎细胞因子的分泌，而ITAMa和ITAMi蛋白之间的平衡受到干扰，Fyn和Lyn的激活增强。出乎意料的是，热带利什曼原虫感染而非大利什曼原虫感染引发了FcγRIIA/CD32a的胞质内加工。
我们的观察结果强调了FcγRIIA/CD32a在皮肤利什曼病中的重要性及其作为治疗靶点的潜在用途。
