Laboratório de Biologia Celular, Instituto Oswaldo Cruz (FIOCRUZ), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Universidade do Estado de Minas Gerais (UEMG), Laboratório de Parasitologia Aplicada, Unidade Passos, Belo Horizonte, Brazil.
Front Cell Infect Microbiol. 2022 May 6;12:882555. doi: 10.3389/fcimb.2022.882555. eCollection 2022.
Chagas disease (CD), caused by the hemoflagellate protozoan , affects more than six million people worldwide and presents an unsatisfactory therapy, based on two nitroderivatives, introduced in clinical medicine for decades. The synthetic peptide, with CTHRSSVVC sequence (PepA), mimics the CD163 and TNF-α tripeptide "RSS" motif and binds to atheromatous plaques in carotid biopsies of human patients, spleen tissues, and a low-density lipoprotein receptor knockout (LDLr-/-) mouse model of atherosclerosis. CD163 receptor is present on monocytes, macrophages, and neutrophils, acting as a regulator of acute-phase processes and modulating aspects of the inflammatory response and the establishment of infections. Due to the potential theranostic role of PepA, our aim was to investigate its effect upon infection and . PepA and two other peptides with shuffled sequences were assayed upon different binomials of host cell/parasite, including professional [as peritoneal mouse macrophages (PMM)] and non-professional phagocytes [primary cultures of cardiac cells (CM)], under different protocols. Also, their impact was further addressed using a mouse model of acute experimental Chagas disease. Our findings demonstrate that PepA and PepB (the peptide with random sequence retaining the "RS" sequence) reduced the intracellular parasitism of the PMM but were inactive during the infection of cardiac cells. Another set of and studies showed that they do not display a trypanocidal effect on bloodstream trypomastigotes nor exhibit efficacy when administered after the parasite inoculation. Our data report the activity of PepA and PepB upon the infection of PMM by , possibly triggering the microbicidal arsenal of the host professional phagocytes, capable of controlling parasitic invasion and proliferation.
恰加斯病（CD）是由血鞭毛原生动物引起的，影响着全球六百多万人，并且基于两种引入临床几十年的硝基衍生物，治疗效果并不理想。合成肽，具有 CTHRSSVVC 序列（PepA），模拟了 CD163 和 TNF-α 三肽“RSS”基序，并与人类患者颈动脉活检、脾脏组织和载脂蛋白 E 基因敲除（ApoE-/-）小鼠动脉粥样硬化模型中的动脉粥样斑块结合。CD163 受体存在于单核细胞、巨噬细胞和中性粒细胞上，作为急性期过程的调节剂，调节炎症反应和感染的建立。由于 PepA 具有潜在的治疗诊断作用，我们的目的是研究它对 感染和 的影响。PepA 和两个具有乱序序列的其他肽在不同的宿主细胞/寄生虫二元组合下进行了测试，包括专业的[如腹膜鼠巨噬细胞（PMM）]和非专业的吞噬细胞[心脏细胞（CM）的原代培养]，并采用不同的方案。此外，还在急性实验性恰加斯病小鼠模型中进一步研究了它们的作用。我们的研究结果表明，PepA 和 PepB（保留“RS”序列的随机序列肽）降低了 PMM 的细胞内寄生虫感染，但在心脏细胞感染时无效。另一组 和 研究表明，它们对血流中的锥虫并没有杀锥虫作用，也没有在寄生虫接种后给予时表现出疗效。我们的数据报告了 PepA 和 PepB 对 PMM 感染 的活性，可能触发宿主专业吞噬细胞的杀菌武器，能够控制寄生虫的入侵和增殖。
