Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Biomed Res Int. 2018 Nov 12;2018:5693736. doi: 10.1155/2018/5693736. eCollection 2018.
Activation of toll-like receptors (TLRs) has been shown to play an important role in leishmaniosis by enhancing the parasite specific immune responses to control infection. However, the role of TLR agonists has not been studied in detail in dogs. The aim of this study was to determine the effect of TLR3, TLR4, and TLR7 agonists (TLR3a, TLR4a, and TLR7a) alone or in combination with antigen (LSA) on TNF- and IL-6 production in blood from dogs living in endemic areas of canine leishmaniosis (CanL). Twenty-four healthy dogs from Catalonia (n=14) and Ibizan hound dogs from the island of Mallorca (n=10) were enrolled. Whole blood with TLR3a, TLR4a, and TLR7a alone or combined with LSA were cultured separately, and IFN-, TNF-, and IL-6 were measured by ELISA. A significant increase of TNF- was found for all conditions studied compared to medium alone. Stimulation with TLR4a and TLR7a presented a significantly marked increase in TNF- and IL-6 production compared to TLR3a. Importantly, significantly higher TNF- production was found in LSA+TLR4a stimulated blood and LSA+TLR7a compared to LSA alone. All dogs showed higher TNF- production after LSA+TLR7a compared to TLR7a and LSA+TLR3a compared to TLR3a . These data indicate a marked inflammatory cytokine effect of TLR4a and TLR7a on blood from healthy dogs living in endemic areas of CanL. Additionally, LSA+TLR7a promoted a synergistic proinflammatory effect with TNF- in all dogs. Those findings suggest an active role of TLRs in proinflammatory responses, which might be strongly involved in the process of disease resolution.
TLR 激活被证实通过增强寄生虫特异性免疫反应来控制感染，在利什曼病中发挥重要作用。然而，TLR 激动剂在犬中的作用尚未得到详细研究。本研究旨在确定 TLR3、TLR4 和 TLR7 激动剂（TLR3a、TLR4a 和 TLR7a）单独或与抗原（LSA）联合应用对来自利什曼病流行地区的犬血液中 TNF-α 和 IL-6 产生的影响。本研究纳入了来自加泰罗尼亚的 24 只健康犬（n=14）和来自马略卡岛的伊比沙猎犬（n=10）。单独培养 TLR3a、TLR4a 和 TLR7a 以及 TLR3a 与 LSA 联合培养全血，通过 ELISA 测量 IFN-、TNF-α 和 IL-6。与单独培养基相比，所有研究条件下均发现 TNF-α 显著增加。与 TLR3a 相比，TLR4a 和 TLR7a 的刺激呈现出 TNF-α 和 IL-6 产生的显著增加。重要的是，与单独的 LSA 相比，在 LSA+TLR4a 刺激的血液和 LSA+TLR7a 中发现 TNF-α 产生显著增加。与 TLR7a 相比，所有犬在 LSA+TLR7a 后 TNF-α 产生更高，与 TLR3a 相比，LSA+TLR3a 后 TNF-α 产生更高。这些数据表明 TLR4a 和 TLR7a 在来自利什曼病流行地区的健康犬血液中具有明显的促炎细胞因子作用。此外，LSA+TLR7a 在所有犬中促进了与 TNF-α 的协同促炎作用。这些发现表明 TLR 在促炎反应中发挥积极作用，这可能与疾病的缓解过程密切相关。
