Ávila Leslye T, Galué-Parra Adan J, Moraes Lienne S, Hage Amanda A P, Rodrigues Ana P D, Farias Luis H S, Sena Chubert B C, Sampaio Sandra C, da Silva Edilene Oliveira
Laboratory of Structural Biology, Federal University of Para, Institute of Biological Sciences, Belém, Pará 66075-110, Brazil.
Postgraduate Program in Biology of Infectious and Parasitic Agents, Federal University of Para Institute of Biological Sciences, Belém, Pará 66075-110, Brazil.
ACS Omega. 2025 Jul 23;10(30):33619-33628. doi: 10.1021/acsomega.5c04319. eCollection 2025 Aug 5.
spp. is an obligate intracellular parasite that primarily infects macrophages. During infection, leukocytes are activated, culminating in the formation of lipid droplets (LDs), which are sites for the synthesis of eicosanoids that modulate the immune response. Crotoxin (CTX), the major toxin derived from (Cdt) snake venom, exhibits pro-inflammatory properties by promoting LD formation and further eicosanoid production. The aim of the present study was to analyze the effects of CTX on the formation of LDs in uninfected and -infected macrophages. Cells were treated with CTX (2.4 and 4.8 μg/mL) and infected or not with parasites, before analyzing LD formation. The kinetic effect of CTX in uninfected macrophages demonstrated a time-dependent and progressive formation of LDs. CTX inhibited the accumulation of LDs during the first 12 h of infection and reduced the parasite load. Ultrastructural analysis revealed different electron densities and sizes of LDs in or near the parasitophore vacuole, indicating that LDs are used by the parasite. Increased levels of prostaglandin E2 (PGE2) also indicated the utilization of LDs by infected macrophages after CTX treatment. CTX stimulated the production of lipid-derived proinflammatory molecules by macrophages, thereby killing the parasite.
某些种属是专性细胞内寄生虫，主要感染巨噬细胞。在感染过程中，白细胞被激活，最终形成脂滴（LDs），脂滴是合成调节免疫反应的类花生酸的场所。响尾蛇毒素（CTX）是从（Cdt）蛇毒中提取的主要毒素，通过促进脂滴形成和进一步产生类花生酸而具有促炎特性。本研究的目的是分析CTX对未感染和感染巨噬细胞中脂滴形成的影响。在分析脂滴形成之前，用CTX（2.4和4.8μg/mL）处理细胞，并使其感染或不感染寄生虫。CTX在未感染巨噬细胞中的动力学效应表明脂滴呈时间依赖性和渐进性形成。CTX在感染的最初12小时内抑制了脂滴的积累，并降低了寄生虫载量。超微结构分析显示，在寄生泡内或附近的脂滴具有不同的电子密度和大小，表明脂滴被寄生虫利用。前列腺素E2（PGE2）水平的升高也表明CTX处理后感染的巨噬细胞利用了脂滴。CTX刺激巨噬细胞产生脂质衍生的促炎分子，从而杀死寄生虫。
