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血吸虫病患者树突状细胞对巴西利什曼原虫感染的易感性。

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis.

作者信息

Lopes Diego Mota, de Almeida Tarcísio Vila Verde S, de Souza Robson da Paixão, Ribeiro Luís Eduardo Viana, Page Brady, Fernandes Jamille de Souza, Carvalho Edgar M, Cardoso Luciana Santos

机构信息

Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT- DT) -CNPQ/MCT, Brazil.

Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil.

出版信息

Mol Immunol. 2018 Jan;93:173-183. doi: 10.1016/j.molimm.2017.11.018. Epub 2017 Nov 29.

Abstract

Coinfection with leishmaniasis and schistosomiasis has been associated with increased time to healing of cutaneous lesions of leishmaniasis. The objective of this study was to evaluate the effect of Leishmania braziliensis infection on co-cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes from patients with schistosomiasis and patients with cutaneous leishmaniasis. MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic beads, infected with L. braziliensis, and co-cultured with autologous lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10 receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on lymphocytes were evaluated by flow cytometry. The production of the cytokines IL-10, TNF, IL-12p40, and IFN-γ were evaluated by sandwich ELISA of the culture supernatant. The infectivity evaluation was performed by light microscopy after concentration of cells by cytospin and Giemsa staining. It was observed that the frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR were smaller in the group of patients with schistosomiasis compared to the group of patients with leishmaniasis. On the other hand, the frequency of IL-10R on MoDCs was higher in patients with schistosomiasis than in patients with leishmaniasis. CD4 and CD8 T lymphocytes from patients with schistosomiasis presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the supernatants of co-cultures from individuals with schistosomiasis compared to those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-γ were lower in the group of individuals with schistosomiasis. Regarding the frequency of MoDCs infected by L. braziliensis after 72h in culture, it was observed that higher frequencies of cells from patients with schistosomiasis were infected compared to cells from patients with leishmaniasis. It was concluded that MoDCs from patients with schistosomiasis are more likely to be infected by L. braziliensis, possibly due to a lower degree of activation and a regulatory profile.

摘要

利什曼病和血吸虫病的合并感染与利什曼病皮肤病变愈合时间延长有关。本研究的目的是评估巴西利什曼原虫感染对来自血吸虫病患者和皮肤利什曼病患者的单核细胞衍生树突状细胞(MoDCs)与自体淋巴细胞共培养的影响。MoDCs由外周血单核细胞分化而来,通过磁珠分离,感染巴西利什曼原虫,并与自体淋巴细胞共培养。通过流式细胞术评估MoDCs上HLA-DR、CD1a、CD83、CD80、CD86、CD40和白细胞介素-10受体(IL-10R)以及淋巴细胞上CD28、CD40L、CD25和细胞毒性T淋巴细胞相关抗原4(CTLA-4)的表达。通过夹心ELISA检测培养上清液中细胞因子IL-10、肿瘤坏死因子(TNF)、白细胞介素-12p40和干扰素-γ(IFN-γ)的产生。通过细胞离心涂片法浓缩细胞并进行吉姆萨染色后,用光学显微镜进行感染性评估。观察到,与皮肤利什曼病患者组相比,血吸虫病患者组中表达CD83、CD80和CD86的MoDCs频率以及HLA-DR的平均荧光强度(MFI)较小。另一方面,血吸虫病患者MoDCs上IL-10R的频率高于皮肤利什曼病患者。与皮肤利什曼病患者的淋巴细胞相比,血吸虫病患者的CD4和CD8 T淋巴细胞呈现较低的CD28频率和较高的CTLA-4频率。与皮肤利什曼病患者相比,血吸虫病患者共培养上清液中IL-10水平更高。然而,血吸虫病患者组中TNF、IL-12p40和IFN-γ水平较低。关于培养72小时后被巴西利什曼原虫感染的MoDCs频率,观察到与皮肤利什曼病患者的细胞相比,血吸虫病患者的细胞被感染的频率更高。得出的结论是,血吸虫病患者的MoDCs更有可能被巴西利什曼原虫感染,这可能是由于激活程度较低和具有调节特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9348/6203323/a34874906c12/nihms-992559-f0001.jpg

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