Table_1_Leishmania braziliensis Subverts Necroptosis by Modulating RIPK3 Expression.DOCX

Leishmania braziliensis infection causes skin ulcers, typically found in localized cutaneous leishmaniasis (LCL). This tissue pathology associates with different modalities of cell necrosis, which are subverted by the parasite as a survival strategy. Herein we examined the participation of necroptosis, a specific form of programmed necrosis, in LCL lesions and found reduced RIPK3 and PGAM5 gene expression compared to normal skin. Assays using infected macrophages demonstrated that the parasite deactivates both RIPK3 and MLKL expression and that these molecules are important to control the intracellular L. braziliensis replication. Thus, LCL-related necroptosis may be targeted to control infection and disease immunopathology.

利什曼原虫巴西亚种感染可导致皮肤溃疡，通常见于局限型皮肤利什曼病（LCL）。此类组织病理学变化与细胞坏死的多种形式相关联，而这些形式被寄生虫作为一种生存策略所篡改。在本研究中，我们探讨了坏死性凋亡，一种特定的程序性坏死形式，在LCL病变中的作用，并发现与正常皮肤相比，RIPK3和PGAM5基因表达降低。使用受感染巨噬细胞的实验表明，寄生虫会抑制RIPK3和MLKL的表达，而这些分子对于控制利什曼原虫在细胞内的复制至关重要。因此，针对与LCL相关的坏死性凋亡可能成为控制感染和疾病免疫病理学的一种策略。