Bomfim Lays G S, Magalhães Lucas S, Santos-Filho Marcello A A, Peres Nalu T A, Corrêa Cristiane B, Tanajura Diego M, Silva Angela M, Lipscomb Michael W, Borges Valéria M, Jesus Amélia R, Almeida Roque P, de Moura Tatiana R
Laboratório de Biologia Molecular-Hospital Universitário, Universidade Federal de Sergipe-Aracaju, Sergipe, Brazil.
Department of Biology, Howard University, Washington, DC, United States.
Front Microbiol. 2017 Nov 16;8:2265. doi: 10.3389/fmicb.2017.02265. eCollection 2017.
Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure to modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.
内脏利什曼病（VL）是一种全身性传染病，仍然是一个主要的全球健康问题。VL期间的炎症反应以多种细胞因子和其他促炎介质的释放为特征。髓系细胞表达的触发受体（TREM）是一组在中性粒细胞和单核细胞上表达的进化保守的膜结合表面受体。TREM-1的激活引导细胞内信号事件，驱动细胞因子产生、脱颗粒和吞噬作用。在某些炎症相关疾病中，TREM-1也可以以可溶性形式（sTREM-1）存在，它可以负向调节TREM-1受体信号。在这些研究中，我们现在发现循环中高水平的sTREM-1与VL疾病严重程度直接相关。特别是，在非存活的VL患者中观察到高水平的sTREM-1。此外，这些sTREM-1水平与肝脏大小呈正相关，与白细胞计数和血红蛋白浓度呈负相关。而且，我们发现中性粒细胞暴露于 可调节TREM-1、DAP12和IL-8基因表达，同时也增加sTREM-1的释放。最后，结果显示较高的sTREM-1水平与寄生虫比例增加有关。综上所述，这些研究表明 可能调节中性粒细胞中的TREM-1，并且该分子的高水平与严重的VL相关。 （原文中“neutrophils exposure to modulates”部分有缺失内容）
