Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Hum Immunol. 2010 Dec;71(12):1220-7. doi: 10.1016/j.humimm.2010.09.002. Epub 2010 Sep 18.
Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal inflammatory infiltrate. Diffuse CL (DCL) cases are hyporesponsive, and lesions show very few lymphocytes and a predominance of macrophages. In contrast, localized CL (LCL) cases are responsive to leishmanial antigen, and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases, changing to a pattern with numerous lymphocytes and macrophages later in the lesion. Therefore, different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations. In lesions from LCL patients, we examined by flow cytometry the presence of different chemokines and their receptors in T cells, and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection). We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL. Using immunohistochemistry, we observed a higher expression of CCL7, CCL17 in lesions from late LCL, as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL. Comparing lesions from LCL and DCL patients, we observed a higher frequency of CCL7 in DCL lesions. These results point out the importance of the chemokines, defining the different types of cells recruited to the site of the infection, which could be related to the outcome of infection as well as the clinical form observed.
皮肤利什曼病(CL)包括不同的临床表现,显示出不同强度的皮肤炎症浸润。弥漫性 CL(DCL)病例反应迟钝,病变中淋巴细胞很少,巨噬细胞占优势。相比之下,局限性 CL(LCL)病例对利什曼抗原有反应,病变在早期表现为粒细胞和单核细胞浸润,随后病变中出现大量淋巴细胞和巨噬细胞。因此,不同的趋化因子可能会影响不同临床表现中细胞浸润的优势。在 LCL 患者的病变中,我们通过流式细胞术检查了 T 细胞中不同趋化因子及其受体的存在,并在 LCL 的早期(感染后<30 天)观察到 CXCR3 的表达较高,在疾病的晚期(感染后>60 天)观察到 CCR4 的表达较高。我们还观察到 LCL 晚期 T 细胞产生 IL-10 的频率较高。通过免疫组织化学,我们观察到 LCL 晚期病变中 CCL7、CCL17 和 CCR4 的表达较高,表明在晚期 LCL 中存在调节性 T 细胞的优先募集。比较 LCL 和 DCL 患者的病变,我们观察到 DCL 病变中 CCL7 的频率较高。这些结果表明趋化因子的重要性,决定了感染部位募集的不同类型的细胞,这可能与感染的结果以及观察到的临床形式有关。
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