Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Immunology. 2024 Mar;171(3):413-427. doi: 10.1111/imm.13736. Epub 2023 Dec 27.
Toll-like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll-like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4 CXCR5 PD-1 Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down-regulated expression of functional molecules CD40L, IFN-γ, IL-21 and IL-10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM-infected mice.
Toll 样受体（TLRs）在诱导针对感染的先天和获得性免疫反应中发挥重要作用。然而，Toll 样受体 7（TLR7）对感染疟原虫的小鼠滤泡辅助 T（Tfh）细胞的影响尚不清楚。结果表明，感染疟原虫 yoelii NSM 后，脾脏 CD4+CXCR5+PD-1+Tfh 细胞积聚，脾脏 Tfh 细胞的含量与寄生虫血症和/或血液中红细胞（RBC）计数相关。此外，在 WT 小鼠的脾脏 Tfh 细胞中发现 TLR7 的表达高于 TLR2、TLR3 和 TLR4。TLR7 激动剂 R848 和感染小鼠的红细胞裂解物（iRBCs）可诱导脾脏 Tfh 细胞的激活和分化。TLR7 敲除导致 Tfh 细胞比例降低，Tfh 细胞中功能性分子 CD40L、IFN-γ、IL-21 和 IL-10 的表达下调；浆细胞比例和抗体产生减少，Tfh 细胞中 STAT3 和 Ikzf2 的表达降低。给予 R848 可抑制寄生虫血症，增强脾脏 Tfh 细胞的激活，并增加 Tfh 细胞中 STAT3 和 Ikzf2 的表达。总之，本研究表明 TLR7 可调节 Tfh 细胞的功能，影响疟原虫 yoelii NSM 感染小鼠脾脏中的免疫反应。
Front Cell Infect Microbiol. 2021
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