sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.
sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.
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DOI：
10.1371/journal.pntd.0005486
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发表时间：
2017-03
影响因子：
3.8
通讯作者：
Jesus AR
中科院分区：
文献类型：
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作者：
Silva RL;Santos MB;Almeida PL;Barros TS;Magalhães L;Cazzaniga RA;Souza PR;Luz NF;França-Costa J;Borges VM;Lima-Junior DS;Lipscomb MW;Duthie MS;Reed SG;Almeida RP;Jesus AR
CD163是接触红蛋白-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。CD163的可溶性形式（sCD163）与M2巨噬细胞表型相关，M2巨噬细胞已被证明可以下调炎症反应。特别是，以往的研究表明，M2与麻风病最严重的临床表现（即麻风性麻风病（LL））以及结核病密切相关。我们假设sCD163与细胞内病原体引起的疾病的严重程度相关。为了评估这一假设，根据临床表现的严重程度对麻风病和内脏利什曼病（VL）患者的血清中sCD163水平进行了测量。这些疾病患者的sCD163水平明显高于健康对照个体。对麻风病和VL患者感染和疾病状况的进一步分析显示，sCD163水平与疾病严重程度的临床参数明显相关。体外培养实验显示，利什曼原虫感染诱导单核/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。FACS分析显示，表达CD163的细胞同时产生TNF-α和IL-4。综上所述，我们的研究结果表明sCD163是细胞内病原体麻风分枝杆菌和利什曼原虫引起的疾病严重程度的潜在生物标志物，具有调节作用，具有TNF-α释放诱导的炎症性质，但可能诱导与IL-4释放相关的抗炎T细胞反应。内脏利什曼病（VL）是一种系统性的、最严重的利什曼病。可溶性CD163 （sCD163）水平可以作为几种炎症性疾病严重程度的生物标志物。然而，没有报告其与利什曼原虫感染的关系。我们现在首次证明，sCD163在VL患者中增加，它的存在与疾病严重程度的临床参数直接相关。在单核细胞源性巨噬细胞和中性粒细胞体外感染婴儿乳杆菌和亚马孙乳杆菌的实验中，卡介苗可降低巨噬细胞表面CD163的表达，且sCD163的存在在临床改善过程中有所减少。综上所述，这些结果揭示了sCD163在疾病进展过程中的免疫调节中的重要作用，并提示了作为确定疾病严重程度和清除的生物标志物的潜在作用。
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. 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. 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. Visceral leishmaniasis (VL) is a systemic, and most severe form of leishmaniasis. Soluble CD163 (sCD163) levels can serve as biomarker for disease severity in several inflammatory disorders. However, no linkage has been reported for its relationship with Leishmania infections. We now demonstrate, for the first time, that sCD163 is increased in VL patients, and its presence is directly correlated to clinical parameters of disease severity. In vitro infection of monocyte-derived macrophages and neutrophils with L. infantum and L. amazonensis induces, while BCG reduce the expression of CD163 on macrophage surface Furthermore, presence of sCD163 is reduced during clinical improvements. Taken together, results reveal an important role for sCD163 in immune modulation during disease progression, and suggest a potential role as biomarker for determining disease severity and clearance.