Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.
Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica.
复制标题
阻断 PD-1 信号传导可增强日本血吸虫病小鼠的 Th2 细胞反应并加重肝脏免疫病理学。
DOI：
10.1371/journal.pntd.0005094
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发表时间：
2016-10
影响因子：
3.8
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Zhou S;Jin X;Li Y;Li W;Chen X;Xu L;Zhu J;Xu Z;Zhang Y;Liu F;Su C
全世界有超过2.2亿人慢性感染结核杆菌，导致严重疾病甚至死亡。血吸虫病的主要病理损害是虫卵引起的肉芽肿性炎症反应和肝纤维化。炎症反应受到严格控制，并与免疫抑制调节平行，持续维持免疫稳态并限制重要宿主器官中的过度免疫病理损伤。众所周知，程序性死亡1（PD-1）信号传导的激活导致T细胞功能的显著抑制。然而，PD-1信号转导在调节CD 4 + T细胞应答和巨噬细胞感染期间的免疫病理学中的作用尚未确定。在这里，我们发现PD-1在日本血吸虫（S.日本血吸虫）感染的患者。我们还发现，在S.日本血吸虫感染最后，我们发现PD-1信号的阻断增强了CD 4+辅助性T细胞2（Th 2）的反应，并导致了S.日本血吸虫感染，而不减少产卵或沉积在宿主肝脏。总的来说，我们的研究表明，PD-1信号传导被特异性诱导，以控制Th 2相关的炎症反应，并有利于PD-1为基础的肝脏免疫病理学控制的发展。血吸虫病是一种寄生虫病，影响约2.2亿人，主要在（亚）热带地区造成严重的发病率和经济问题。日本血吸虫或曼氏血吸虫感染后，寄生虫卵被困在宿主肝脏中并诱发肝脏炎症和纤维化，导致不可逆的肝脏损伤，甚至导致宿主死亡。同时，脂质体还诱导强调节机制以抑制炎症和防止过度免疫病理学。考虑到众所周知PD-1在抑制T细胞功能中起着关键作用，理解PD-1在介体感染期间调节免疫应答中的作用对于开发基于PD-1的血吸虫病肝损伤控制是必要的。在此，显示了在来自人和小鼠的具有嗜热小体感染的CD 4 + T细胞中增加的PD-1表达。我们进一步表明，PD-1阻断优先增强Th 2细胞应答，并最终导致日本血吸虫小鼠更严重的肝脏免疫病理学，这表明PD-1信号传导有利于进一步探索预防过度肝脏免疫病理学的治疗可能性。
More than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1) signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined. Here, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum)-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2) cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver. Overall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology. Schistosomiasis is a parasitic disease that affects approximately 220 million people and causes serious morbidity and economic problems mainly in (sub)tropical regions. After Schistosoma japonicum or Schistosoma mansoni infection, parasite eggs are trapped in host liver and induce liver inflammation and fibrosis, leading to irreversible impairment of the liver, and even death of the host. Meanwhile, schistosomes also induce strong regulatory mechanisms to suppress inflammation and prevent excessive immunopathology. Considering it is well known that PD-1 plays a critical role in suppressing T cell function, understanding the role of PD-1 in modulating immune responses during schistosome infection is necessary for the development of PD-1-based control of liver damage in schistosomiasis. Here, increased PD-1 expression in CD4+ T cells from both humans and mice with schistosome infection was shown. We further showed that PD-1 blockade preferentially augmented Th2 cell responses and ultimately resulted in more severe liver immunopathology in mice with Schistosomiasis japonica, suggesting that PD-1 signaling is beneficial to further explore therapeutic possibilities for preventing the excessive liver immunopathology.
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影响因子：
4.5
作者：
Boamah D;Kikuchi M;Huy NT;Okamoto K;Chen H;Ayi I;Boakye DA;Bosompem KM;Hirayama K
通讯作者：
Hirayama K
影响因子：
7.3
作者：
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通讯作者：
Fallon PG
影响因子：
7.8
作者：
Kulpa DA;Lawani M;Cooper A;Peretz Y;Ahlers J;Sékaly RP
通讯作者：
Sékaly RP
克服感染和癌症中的T细胞耗尽。
影响因子：
16.8
作者：
Pauken KE;Wherry EJ
通讯作者：
Wherry EJ
TLR2 指导 PD-L2 表达抑制日本血吸虫感染中的 T 细胞反应。
影响因子：
3.7
作者：
Gao Y;Chen L;Hou M;Chen Y;Ji M;Wu H;Wu G
通讯作者：
Wu G