Department of Dermatology and Venerology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Front Immunol. 2023 Jan 12;13:1063443. doi: 10.3389/fimmu.2022.1063443. eCollection 2022.
It has long been recognized that inflammation to dermatophyte infection is different among various hosts, but the mechanism underlying is still not well understood. Toll-like receptor (TLR2), mediates the innate immune response against dermatophyte infection and is very important to trigger the inflammatory response to dermatophytes. Considering the different amino acid sequences and structures of TLR2, we speculated that TLR2 from different hosts will activate the downstream signal pathways to varying degrees, resulting in different inflammatory responses to dermatophytes.
In this study, we constructed the mice-human fusion TLR2 expressed HaCaT (mhTLR2-HaCaT) by replacing the extracellular ligand recognition region of human TLR2 with that of the mouse. Then hTLR2-HaCaT cells and mhTLR2-HaCaT cells were infected with T. rubrum and M. canis for 24 h followed by immunoblotting to asses associated proteins of p38 and JNK signal pathway.
Compared with that of human TLR2 expressed HaCaT (hTLR2-HaCaT), levels of phosphorylated p38 protein were increased in mhTLR2-HaCaT cells stimulated by T. rubrum for 24 h, and levels of phosphorylatedJNK and c-Jun protein were increased in mhTLR2-HaCaT cells whenstimulated with M. canis for 24 h.
Compared with hTLR2-HaCaT cells, p38 and JNK signal pathwayswere activated in mhTLR2-HaCaT after being infected by Trichophyton rubrumand Microsporum canis, respectively. Since p38 and JNK are the mainpathways that transduce the signal for host recognition of dermatophytes andmediate the downstream inflammatory response, it suggested that theinterspecific difference of TLR2 ectodomain may be one of the reasons for thedifferent inflammatory manifestations between humans and mice infected bythese two dermatophytes. Quite especially, the mouse-derived TLR2extracellular recognition region is more effective in recognizing T. rubrum andM. canis to activate the downstream signal pathways, resulting in a tenserinflammatory response against these two dermatophytes.
长期以来，人们已经认识到，不同宿主对真菌（ Dermatophyte ）感染的炎症反应存在差异，但其中的机制尚不清楚。Toll 样受体（TLR2）介导宿主对真菌感染的固有免疫反应，对于引发对真菌的炎症反应非常重要。鉴于 TLR2 的氨基酸序列和结构存在差异，我们推测不同宿主的 TLR2 会在不同程度上激活下游信号通路，从而导致对真菌的炎症反应不同。
在这项研究中，我们通过用人 TLR2 的胞外配体识别区替换小鼠 TLR2 的胞外配体识别区，构建了小鼠-人融合 TLR2 表达的 HaCaT（mhTLR2-HaCaT）。然后用红色毛癣菌（ T. rubrum ）和须癣毛癣菌（ M. canis ）感染 hTLR2-HaCaT 细胞和 mhTLR2-HaCaT 细胞 24 小时后，通过免疫印迹法评估 p38 和 JNK 信号通路的相关蛋白。
与 hTLR2-HaCaT 细胞相比，mhTLR2-HaCaT 细胞在被 T. rubrum 刺激 24 小时后，磷酸化 p38 蛋白的水平升高，而当 mhTLR2-HaCaT 细胞被 M. canis 刺激 24 小时后，磷酸化 JNK 和 c-Jun 蛋白的水平升高。
与 hTLR2-HaCaT 细胞相比，mhTLR2-HaCaT 细胞在被红色毛癣菌和须癣毛癣菌感染后，p38 和 JNK 信号通路分别被激活。由于 p38 和 JNK 是宿主识别真菌和介导下游炎症反应的主要信号转导途径，这表明 TLR2 胞外结构域的种间差异可能是这两种真菌引起人和小鼠炎症表现不同的原因之一。特别是，源自小鼠的 TLR2 胞外识别区更有效地识别 T. rubrum 和 M. canis，以激活下游信号通路，导致对这两种真菌产生紧张的炎症反应。
