Departamento de Patologia Geral, Faculdade de Medicina, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, Minas Gerais, Brazil.
BMC Immunol. 2013 May 14;14:22. doi: 10.1186/1471-2172-14-22.
Infection with parasite protozoa is a long-term health issue in tropical and subtropical regions throughout the world. The Toll-like receptor (TLR) signaling pathway is one of the first-responding defense systems against Leishmania. The aim of this study was to investigate the expression of TLR2 and TLR9 in jejunum and colon and its correlation with CD11c, CD11b, and CD14 receptors used as markers for dendritic cells and macrophages.
Twenty four dogs infected with Leishmania infantum were used in this study. Cytometry was carried out in lamina propria cells from jejunum and colon using markers for TLR2, TLR9, CD11b, CD11c and CD14.
Cellular inflammatory exudate was diffuse in the mucosa and submucosa, predominately comprising mononuclear cells: plasma cells, macrophages, and lymphocytes. Despite the parasite load, microscopy showed no erosion was evident in the epithelial mucosa layers. The colon harbored more parasites than the jejunum. Flow cytometry revealed higher frequency of TLR2+ and CD11c+ dendritic cells in the colon than in the jejunum. Conversely, TLR9-expressing cells were more frequent in jejunum. Moreover, frequency of macrophages (CD11b+ and CD14+) expressing simultaneity TLR9 were lower in the colon than in jejunum, while CD11c+ cells predominated in the colon. Despite of the negative ELISA serum results, IL-10 and TNF-α were higher in jejunum than colon of infected animals. However, IL-4 was higher in colon than jejunum of infected animals. A higher expression these cytokines were demonstrated in infected dogs compared to uninfected dogs.
There was no correlation between clinical signs and pathological changes and immunological and parasitological findings in the gastrointestinal tract in canine visceral leishmaniasis. However, jejunum showed a lower parasite load with increased frequency and expression of CD11b, TLR9, CD14/CD11b/TLR9 receptors and IL-10 and TNF-α cytokines. Conversely, the colon showed a higher parasite load along with increased frequency and expression of TLR2, CD11c receptors, and IL-4 cytokine. Thus, Leishmania infantum is able to interfere in jejunum increased expression of TLR2, TLR9, CD11b, CD14, CD14/CD11b/TLR9 receptors, IL-10, and TNF-α; and in colon increased expression of CD11c, TLR2, TLR9, CD11b, CD14 e, CD14/CD11b/TLR9 receptors, IL-10, and TNF-α.
寄生虫原生动物的感染是世界范围内热带和亚热带地区的一个长期健康问题。Toll 样受体(TLR)信号通路是对利什曼原虫的第一道防御系统之一。本研究的目的是研究 TLR2 和 TLR9 在空肠和结肠中的表达及其与用作树突状细胞和巨噬细胞标志物的 CD11c、CD11b 和 CD14 受体的相关性。
本研究使用 24 只感染利什曼原虫的犬。使用 TLR2、TLR9、CD11b、CD11c 和 CD14 标志物对空肠和结肠的固有层细胞进行细胞仪分析。
黏膜和黏膜下层弥漫性出现细胞性炎症渗出物,主要由单核细胞组成:浆细胞、巨噬细胞和淋巴细胞。尽管寄生虫负荷量很大,但显微镜检查显示上皮黏膜层没有明显的侵蚀。结肠比空肠含有更多的寄生虫。流式细胞术显示,结肠中 TLR2+和 CD11c+树突状细胞的频率高于空肠。相反,TLR9 表达细胞在空肠中更为常见。此外,结肠中同时表达 TLR9 的巨噬细胞(CD11b+和 CD14+)频率低于空肠,而 CD11c+细胞在结肠中占优势。尽管血清 ELISA 结果为阴性,但感染动物的空肠中 IL-10 和 TNF-α 高于结肠。然而,感染动物的结肠中 IL-4 高于空肠。与未感染的犬相比,感染犬的这些细胞因子表达水平更高。
在犬内脏利什曼病的胃肠道中,临床症状和病理变化与免疫学和寄生虫学发现之间没有相关性。然而,空肠的寄生虫负荷较低,CD11b、TLR9、CD14/CD11b/TLR9 受体以及 IL-10 和 TNF-α 细胞因子的频率和表达增加。相反,结肠的寄生虫负荷较高,同时 TLR2、CD11c 受体和 IL-4 细胞因子的频率和表达增加。因此,利什曼原虫能够在空肠中增加 TLR2、TLR9、CD11b、CD14、CD14/CD11b/TLR9 受体、IL-10 和 TNF-α 的表达;在结肠中增加 CD11c、TLR2、TLR9、CD11b、CD14e、CD14/CD11b/TLR9 受体、IL-10 和 TNF-α 的表达。