Silva Ricardo Luís Louzada, Santos Marcio B, Almeida Priscila L S, Barros Thayse S, Magalhães Lucas, Cazzaniga Rodrigo A, Souza Patrícia R M, Luz Nívea F, França-Costa Jaqueline, Borges Valeria M, Lima-Junior Djalma S, Lipscomb Michael W, Duthie Malcolm S, Reed Steven G, Almeida Roque Pacheco, Jesus Amélia Ribeiro
Laboratório de Biologia Molecular-Hospital Universitário-Universidade Federal de Sergipe-Aracaju-Brazil.
Departamento de Educação em Saúde de Lagarto-Universidade Federal de Sergipe-Lagarto-Brazil.
PLoS Negl Trop Dis. 2017 Mar 29;11(3):e0005486. doi: 10.1371/journal.pntd.0005486. eCollection 2017 Mar.
CD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens.
METHODOLOGY/PRINCIPAL FINDINGS: To assess this hypothesis, sCD163 levels were measured in the serum of leprosy and visceral leishmaniasis (VL) patients stratified by severity of the clinical presentation. sCD163 levels were significantly higher in patients with these diseases than those observed in healthy control individuals. Further analyses on infection and disease status of leprosy and VL patients revealed a clear association of sCD163 levels with clinical parameters of disease severity. In vitro culture assays revealed that Leishmania infection induced CD163 expression on the surface of both monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163. FACS analyses shows that the cells expressing CD163 produces both TNF-α and IL-4.
CONCLUSIONS/SIGNIFICANCE: Taken together, our results reveal sCD163 as a potential biomarker of severity of diseases caused by intracellular pathogens M. leprae and Leishmania spp. and have a modulatory role, with a mix of an inflammatory property induced by TNF-α release, but that potentially induces an anti-inflammatory T cell response, related to IL-4 release.
CD163是触珠蛋白-血红蛋白复合物的受体，在单核细胞/巨噬细胞和中性粒细胞上表达。可溶性CD163（sCD163）与M2巨噬细胞表型相关，且已表明M2巨噬细胞可下调炎症反应。特别是，先前的研究表明M2与麻风病（即瘤型麻风（LL））以及结核病最严重的临床表现密切相关。我们推测sCD163与细胞内病原体引起的疾病严重程度相关。
方法/主要发现：为评估这一假设，我们检测了按临床表现严重程度分层的麻风病和内脏利什曼病（VL）患者血清中的sCD163水平。这些疾病患者的sCD163水平显著高于健康对照个体。对麻风病和VL患者的感染及疾病状态进行的进一步分析显示，sCD163水平与疾病严重程度的临床参数存在明确关联。体外培养试验表明，利什曼原虫感染可诱导单核细胞/巨噬细胞和中性粒细胞表面表达CD163，提示这些细胞可能是sCD163的来源。流式细胞术分析表明，表达CD163的细胞可产生肿瘤坏死因子-α（TNF-α）和白细胞介素-4（IL-4）。
结论/意义：综上所述，我们的结果表明sCD163是由细胞内病原体麻风分枝杆菌和利什曼原虫属引起的疾病严重程度的潜在生物标志物，并且具有调节作用，兼具因TNF-α释放诱导的炎症特性，但可能诱导与IL-4释放相关的抗炎性T细胞反应。
