Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório Interdisciplinar de Pesquisas Médicas, Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio Grande do Norte, Instituto de Medicina Tropical do Rio Grande do Norte, Natal, RN, Brasil.
Mem Inst Oswaldo Cruz. 2023 Mar 27;118:e220044. doi: 10.1590/0074-02760220044. eCollection 2023.
Dendritic cells (DCs) specific intercellular adhesion molecule (ICAM)-3-grabbing non integrin receptor (DC-SIGN) binds to subgenera Leishmania promastigotes mediating its interaction with DC and neutrophils, potentially influencing the infection outcome.
In this work, we investigated whether DC-SIGN receptor is expressed in cells from cutaneous leishmaniasis (CL) lesions as well as the in vitro binding pattern of Leishmania (Viannia) braziliensis (Lb) and L. (L.) amazonensis (La) promastigotes.
DC-SIGN receptor was labeled by immunohistochemistry in cryopreserved CL tissue fragments. In vitro binding assay with CFSE-labeled Lb or La promastigotes and RAJI-transfecting cells expressing DC-SIGN (DC-SIGNPOS) or mock-transfected (DC-SIGNNEG) were monitored by flow cytometry at 2 h, 24 h and 48 h in co-culture.
In CL lesion infiltrate, DC-SIGNPOS cells were present in the dermis and near the epidermis. Both Lb and La bind to DC-SIGNPOS cells, while binding to DC-SIGNNEG was low. La showed precocious and higher affinity to DC-SIGNhi population than to DC-SIGNlow, while Lb binding was similar in these populations.
Our results demonstrate that DC-SIGN receptor is present in L. braziliensis CL lesions and interact with Lb promastigotes. Moreover, the differences in the binding pattern to Lb and La suggest DC-SIGN can influence in a difference way the intake of the parasites at the first hours after Leishmania infection. These results raise the hypothesis that DC-SIGN receptor could participate in the immunopathogenesis of American tegumentary leishmaniasis accounting for the differences in the outcome of the Leishmania spp. infection.
树突状细胞（DC）特异性细胞间黏附分子（ICAM）-3 抓取非整合素受体（DC-SIGN）与 Leishmania 前鞭毛体结合，介导其与 DC 和中性粒细胞的相互作用，可能影响感染结局。
本研究旨在探讨 DC-SIGN 受体是否在皮肤利什曼病（CL）病变细胞中表达，以及 Leishmania（Viannia）braziliensis（Lb）和 L.（L.）amazonensis（La）前鞭毛体的体外结合模式。
用免疫组织化学方法标记冷冻保存的 CL 组织片段中的 DC-SIGN 受体。通过流式细胞术监测 CFSE 标记的 Lb 或 La 前鞭毛体与表达 DC-SIGN（DC-SIGNPOS）或 mock 转染（DC-SIGNNEG）的 RAJI 转染细胞在共培养 2 小时、24 小时和 48 小时的体外结合。
在 CL 病变浸润中，DC-SIGNPOS 细胞存在于真皮和表皮附近。Lb 和 La 均可与 DC-SIGNPOS 细胞结合，而与 DC-SIGNNEG 结合较低。与 DC-SIGNlow 相比，La 对 DC-SIGNhi 群体的结合具有更早和更高的亲和力，而 Lb 在前两种群体中的结合相似。
本研究结果表明，DC-SIGN 受体存在于 L. braziliensis CL 病变中，并与 Lb 前鞭毛体相互作用。此外，Lb 和 La 结合模式的差异表明，DC-SIGN 可能以不同的方式影响 Leishmania 感染后最初几小时内寄生虫的摄取。这些结果提出了一个假设，即 DC-SIGN 受体可能参与美洲皮肤利什曼病的免疫发病机制，从而解释了不同 Leishmania spp. 感染结局的差异。
