Laboratory of Molecular Physiology, Institute of Experimental Medicine, School of Medicine Luis Razetti, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela.
Laboratory of Molecular Physiology, Institute of Experimental Medicine, School of Medicine Luis Razetti, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela.
Exp Parasitol. 2020 Dec;219:108009. doi: 10.1016/j.exppara.2020.108009. Epub 2020 Sep 29.
Cell-cell interaction and active migration (and invasion) of parasites into skin host-cell(s) are key steps for successful infection by Leishmania. Chemotaxis constitutes a primordial chapter of Leishmania-host cell interaction, potentially modulated by neuropeptides released into the skin due, for example, to the noxious stimuli represented by the insect bite. Herein we have evaluated in vitro the effect of sensory (Substance P, SP) and autonomic (Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY) neuropeptides on parasite taxis, and investigated the potential modulatory effect of SP on Leishmania (Viannia) braziliensis-macrophage interaction. We demonstrated that VIP (10 M) and NPY (10 M) are chemorepellent to the parasites, while SP (10 M) produces a chemoattractant response. SP did not affect macrophage viability but seems to impair parasite-macrophage interaction as it decreased promastigote adherence to macrophages. As this effect is blocked by ([D-Pro 2, D-Trp7,9]-Substance P (10 M), the observed action may be mediated by neurokinin-1 (NK) transmembrane receptors. VIP and NPY repellent chemotactic effect is impaired by their corresponding receptor antagonists. Additionally, they suggest that SP may be a key molecule to guide promastigote migration towards, and interaction, with dendritic cells and macrophage host cells.
细胞-细胞相互作用和寄生虫主动迁移（和入侵）进入皮肤宿主细胞是利什曼原虫成功感染的关键步骤。趋化作用构成了利什曼原虫-宿主细胞相互作用的原始篇章，可能受到由于昆虫叮咬等有害刺激而释放到皮肤中的神经肽的调节。在此，我们评估了感觉（P 物质，SP）和自主（血管活性肠肽，VIP 和神经肽 Y，NPY）神经肽对寄生虫趋化性的体外影响，并研究了 SP 对利什曼（Viannia）巴西利ensis-巨噬细胞相互作用的潜在调节作用。我们证明 VIP（10 M）和 NPY（10 M）对寄生虫有趋化抑制作用，而 SP（10 M）则产生趋化反应。SP 不影响巨噬细胞活力，但似乎会损害寄生虫-巨噬细胞相互作用，因为它减少了前鞭毛体与巨噬细胞的黏附。由于这种作用被（[D-Pro 2，D-Trp7，9]-P 物质（10 M）阻断，观察到的作用可能是由神经激肽-1（NK）跨膜受体介导的。VIP 和 NPY 的趋化排斥作用被其相应的受体拮抗剂所破坏。此外，它们表明 SP 可能是引导前鞭毛体向树突状细胞和巨噬细胞宿主细胞迁移并相互作用的关键分子。
