Darif Dounia, Desterke Christophe, Hammi Ikram, Kihel Ayyoub, Lemrani Meryem, Riyad Myriam, Akarid Khadija
Biochemistry, Biotechnology and Immunophysiopathology Research Team, Health & Environment Laboratory, Aïn Chock Faculty of Sciences, Hassan II University of Casablanca (UH2C), Morocco; Research Team on Immunopathology of Infectious and Systemic Diseases, Laboratory of Cellular & Molecular Pathology, Faculty of Medicine and Pharmacy, UH2C, Morocco.
Paris-Saclay University, Paul Brousse Hospital, Villejuif, France.
Microb Pathog. 2025 May;202:107414. doi: 10.1016/j.micpath.2025.107414. Epub 2025 Feb 23.
Cutaneous leishmaniasis (CL) is characterized by polymorphic dermal lesions and remains a major public health concern worldwide. This study assessed the impact of different Moroccan Leishmania major strains on host immunopathology. Swiss mice were infected with five L. major strains from Tinghir and Zagora Moroccan endemic foci and sacrificed at 3 and 13 weeks post-infection (p.i). Mice exhibited distinct infection profiles, with lesions appearing between the 2nd and 3rd weeks p.i and stabilizing between the 8th and 12th weeks pi. Two-way ANOVA showed a significant association between lesion size and strain region (p < 0.01), with Zagora strains exhibiting the largest lesions. RT-qPCR analysis revealed that Zagora strains downregulated IL-1β in draining lymph nodes (DLNs) and footpads at 3 and 13 weeks p.i respectively; they also downregulated iNOS in footpads and DLNs at 13 weeks p.i. Unsupervised principal component analysis, integrating lesion size, IL-1β, and iNOS expression with strain region, organ, and infection time, revealed significant associations among these parameters. By integrating these significant parameters, we built a multivariable model with IL-1β quantification as the outcome. This model revealed a positive association of IL-1β with iNOS (p < 0.001), as well as with the spleen (p < 0.001) and footpad (p < 0.01). Conversely, it showed a negative association of IL-1β with the Zagora strains (p < 0.05) and with infection time (13 weeks pi; p < 0.05). Transcriptome analysis highlighted early IL-1β induction in L. major infection, associated with an inflammatory response. Thus, IL-1β and iNOS modulation by L. major strains may explain the clinical polymorphism of CL patients' lesions.
皮肤利什曼病（CL）的特征是出现多形性皮肤病变，在全球范围内仍然是一个主要的公共卫生问题。本研究评估了不同的摩洛哥硕大利什曼原虫菌株对宿主免疫病理学的影响。将瑞士小鼠感染来自摩洛哥廷吉尔和扎戈拉地方病疫源地的5种硕大利什曼原虫菌株，并在感染后3周和13周处死。小鼠表现出不同的感染特征，病变在感染后第2周和第3周之间出现，并在感染后第8周和第12周之间稳定下来。双向方差分析显示病变大小与菌株来源地之间存在显著关联（p < 0.01），扎戈拉菌株的病变最大。逆转录定量聚合酶链反应（RT-qPCR）分析显示，扎戈拉菌株分别在感染后3周和13周下调引流淋巴结（DLN）和足垫中的白细胞介素-1β（IL-1β）；它们还在感染后13周下调足垫和DLN中的诱导型一氧化氮合酶（iNOS）。无监督主成分分析将病变大小、IL-1β和iNOS表达与菌株来源地、器官和感染时间整合在一起，揭示了这些参数之间的显著关联。通过整合这些显著参数，我们构建了一个以IL-1β定量为结果的多变量模型。该模型显示IL-1β与iNOS呈正相关（p < 0.001），与脾脏（p < 0.001）和足垫（p < 0.01）也呈正相关。相反，它显示IL-1β与扎戈拉菌株呈负相关（p < 0.05），与感染时间（感染后13周；p < 0.05）也呈负相关。转录组分析突出了硕大利什曼原虫感染中IL-1β的早期诱导，这与炎症反应相关。因此，硕大利什曼原虫菌株对IL-1β和iNOS的调节可能解释了CL患者病变的临床多态性。
