Institute of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou, China.
J Exp Zool A Ecol Integr Physiol. 2020 Apr;333(4):240-251. doi: 10.1002/jez.2346. Epub 2020 Jan 29.
Ecological immunology involves the study of the immune function of wildlife, which is seldom compared with that of model animals. Here, we evaluated and compared the level of the innate immune response in the plateau zokor (Eospalax baileyi), an indigenous underground rodent from the Tibetan Plateau, with that in the bamboo rat (Rhizomys pruinosus) and Sprague-Dawley (SD) rat (Rattus norvegicus). The spleen was observed by ordinary light and transmission electron microscopy, and the spleen index was calculated. After liposaccharide (LPS) challenge, the expression of Toll-like receptor 2 (TLR2), TLR4, and hypoxia-inducible factor 1α (HIF-1α) in the spleen was detected by Western blot analysis and immunofluorescence. The expression of nuclear factor-κB1 (NF-κB1) and mitogen-activated protein kinase 14 (MAPK14) in the spleen was detected by real-time quantitative polymerase chain reaction, and the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-β (IFN-β) in the spleen were detected by enzyme-linked immunoassay. The spleen index of the plateau zokor was lower than that of the bamboo rat and SD rat. The expression of TLR4, NF-κB1, and MAPK14 and the levels of IL-6 and TNF-α in the spleen of the plateau zokor were lower than those of the bamboo rat and SD rat, while the expression of TLR2 and HIF-1α and the level of IFN-β were higher than those of the bamboo rat and SD rat. We speculate that suppression of the TLR4 signaling pathway in the plateau zokor is an adaptation to hypoxic tunnels that decreases antigenic risk and maintains immune homeostasis. Moreover, the spleen of the plateau zokor is reduced in size, reducing the innate immunity investment in the spleen. We also noted that high levels of HIF-1α in the spleen of the plateau zokor suppressed crosstalk between HIF-1α and TLR4, promoting the innate immune response.
生态免疫学涉及野生动物免疫功能的研究，而野生动物的免疫功能很少与模式动物进行比较。在这里，我们评估和比较了青藏高原鼢鼠（Eospalax baileyi）、竹鼠（Rhizomys pruinosus）和 Sprague-Dawley（SD）大鼠（Rattus norvegicus）的固有免疫反应水平。通过普通光和透射电子显微镜观察脾脏，并计算脾脏指数。用脂多糖（LPS）刺激后，通过 Western blot 分析和免疫荧光检测脾脏中 Toll 样受体 2（TLR2）、TLR4 和缺氧诱导因子 1α（HIF-1α）的表达。通过实时定量聚合酶链反应检测脾脏中核因子-κB1（NF-κB1）和丝裂原活化蛋白激酶 14（MAPK14）的表达，通过酶联免疫吸附试验检测脾脏中白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-β（IFN-β）的水平。青藏高原鼢鼠的脾脏指数低于竹鼠和 SD 大鼠。青藏高原鼢鼠脾脏中 TLR4、NF-κB1 和 MAPK14 的表达以及 IL-6 和 TNF-α的水平低于竹鼠和 SD 大鼠，而 TLR2 和 HIF-1α的表达以及 IFN-β的水平高于竹鼠和 SD 大鼠。我们推测，青藏高原鼢鼠 TLR4 信号通路的抑制是对缺氧隧道的一种适应，降低了抗原风险并维持了免疫稳态。此外，青藏高原鼢鼠脾脏体积减小，减少了脾脏固有免疫的投入。我们还注意到，青藏高原鼢鼠脾脏中高水平的 HIF-1α抑制了 HIF-1α 与 TLR4 之间的串扰，促进了固有免疫反应。
