Kihel Ayyoub, El Filaly Hajar, Darif Dounia, Assouab Aicha, Riyad Myriam, Nait Irahal Imane, Akarid Khadija
Biochemistry, Biotechnology and Immunophysiopathology Research Team, Health and Environment Laboratory, Ain Chock Faculty of Sciences, Hassan II University of Casablanca (UH2C), Casablanca 20100, Morocco.
Immunopathology of Infectious and Systemic Diseases, Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca (UH2C), Casablanca 20000, Morocco.
Microorganisms. 2025 Feb 27;13(3):531. doi: 10.3390/microorganisms13030531.
Leishmaniasis, caused by the parasite, is a neglected public health issue. mainly infects macrophages, where metabolic reprogramming shapes their plasticity (M1/M2), affecting the host's resistance or susceptibility to infection. The development of this infection is influenced by immune responses, with an excessive anti-inflammatory reaction linked to negative outcomes through the modulation of various mediators. Itaconate, produced by the gene, is recognized for its anti-inflammatory effects, but its function in leishmaniasis is not well understood. This study aimed to investigate the potential role of itaconate in leishmaniasis. Using transcriptomic data from -infected BMDMs, we assessed the expression dynamics of and and performed pathway enrichment analysis to determine the profile of genes co-expressed with . Early upregulation followed by later downregulation was noted, indicating a shift towards an anti-inflammatory response. Among the genes co-expressed with , , , and are closely associated with lipid metabolism and the polarization of macrophages towards the M2 phenotype, thereby creating a favorable environment for the survival of . Overall, these findings suggest that and its co-expressed genes may affect the outcome of infection by modulating host metabolism. Accordingly, targeting itaconate-associated pathways could provide a novel therapeutic strategy for leishmaniasis.
利什曼病由寄生虫引起，是一个被忽视的公共卫生问题。它主要感染巨噬细胞，在巨噬细胞中代谢重编程塑造了其可塑性（M1/M2），影响宿主对感染的抵抗力或易感性。这种感染的发展受免疫反应影响，过度的抗炎反应通过多种介质的调节与负面结果相关。由 基因产生的衣康酸因其抗炎作用而被认可，但其在利什曼病中的功能尚不清楚。本研究旨在探讨衣康酸在利什曼病中的潜在作用。利用感染了 的骨髓来源巨噬细胞（BMDMs）的转录组数据，我们评估了 和 的表达动态，并进行了通路富集分析以确定与 共表达的基因谱。注意到 早期上调随后 后期下调，表明向抗炎反应转变。在与 共表达的基因中， 、 、 和 与脂质代谢以及巨噬细胞向M2表型的极化密切相关，从而为 的存活创造了有利环境。总体而言，这些发现表明 及其共表达基因可能通过调节宿主代谢影响 感染的结果。因此，靶向与衣康酸相关的通路可为利什曼病提供一种新的治疗策略。
