Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Infect Immun. 2010 Jan;78(1):301-8. doi: 10.1128/IAI.00959-09. Epub 2009 Nov 9.
Leishmania (subgenus Viannia) braziliensis is the causative agent of mucocutaneous leishmaniasis (ML) in South America, and ML is characterized by excessive T- and B-cell responses to the parasite. We speculate that the unbalanced production of inflammatory mediators in response to L. braziliensis infection contributes to cell recruitment and disease severity. To test this hypothesis, we first examined the response of peripheral blood mononuclear cells (PBMCs) from healthy volunteers to L. braziliensis infection. We observed that while L. braziliensis infection induced the production of chemokine (C-X-C motif) ligand 10 (CXCL10) and interleukin-10 (IL-10) in human PBMCs and macrophages (MPhis), enhanced expression of CXCL10 and its receptor, chemokine CXC receptor (CXCR3), was predominantly detected in CD14(+) monocytes. The chemoattractant factors secreted by L. braziliensis-infected cells were highly efficient in recruiting uninfected PBMCs (predominantly CD14(+) cells) through Transwell membranes. Serum samples from American tegumentary leishmaniasis (ATL) patients (especially the ML cases) had significantly higher levels of CXCL10, CCL4, and soluble tumor necrosis factor (TNF) receptor II (sTNFRII) than did those of control subjects. Our results suggest that, following L. braziliensis infection, the production of multiple inflammatory mediators by the host may contribute to disease severity by increasing cellular recruitment.
巴西利什曼原虫（Viannia 亚属）是南美的黏膜皮肤利什曼病（ML）的病原体，ML 的特征是宿主对寄生虫产生过度的 T 细胞和 B 细胞反应。我们推测，针对 L. braziliensis 感染产生的炎症介质的失衡会导致细胞招募和疾病的严重程度。为了验证这一假说，我们首先检测了来自健康志愿者的外周血单核细胞（PBMCs）对 L. braziliensis 感染的反应。我们观察到，尽管 L. braziliensis 感染诱导了人 PBMCs 和巨噬细胞（MPhis）中趋化因子（C-X-C 基序）配体 10（CXCL10）和白细胞介素 10（IL-10）的产生，但 CXCL10 及其受体趋化因子 CXC 受体（CXCR3）的增强表达主要在 CD14（+）单核细胞中检测到。L. braziliensis 感染细胞分泌的趋化因子因子通过 Transwell 膜非常有效地招募未感染的 PBMCs（主要是 CD14（+）细胞）。美洲皮肤利什曼病（ATL）患者（尤其是 ML 病例）的血清样本中的 CXCL10、CCL4 和可溶性肿瘤坏死因子（TNF）受体 II（sTNFRII）水平明显高于对照组。我们的结果表明，在 L. braziliensis 感染后，宿主产生的多种炎症介质可能通过增加细胞招募来导致疾病的严重程度。
