2. Academic Validation
  3. Porcine TLR8 signaling and its anti-infection function are disturbed by immune checkpoint receptor TIM-3 via inhibition of P13K-AKT pathway

Porcine TLR8 signaling and its anti-infection function are disturbed by immune checkpoint receptor TIM-3 via inhibition of P13K-AKT pathway

  • Int J Biol Macromol. 2024 May 1;269(Pt 1):132018. doi: 10.1016/j.ijbiomac.2024.132018.
Wangli Zheng 1,  Da Ao 2,  Qi Cao 1,  Anjing Liu 1,  Mengjia Lv 1,  Ziyan Sun 1,  Huiling Zhang 3,  Wanglong Zheng 1,  Nanhua Chen 1,  Jianzhong Zhu 4
Affiliations

Affiliations

  • 1 Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China; College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.
  • 2 School of Pharmacy, Changzhou University, Changzhou, Jiangsu 213164, China.
  • 3 Independent person, New York, NY 11355, USA.
  • 4 Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China; College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address: jzzhu@yzu.edu.cn.
PMID: 38702002 DOI: 10.1016/j.ijbiomac.2024.132018
Abstract

Toll-like Receptor 8 (TLR8), an important innate immune receptor recognizing single stranded RNA and the Antiviral imidazoquinoline compounds, can activate intracellular signaling pathway and produce an inflammatory response to kill and eliminate pathogens. However, the molecular regulation mechanisms of TLR8 signaling and its Anti-infection activity are not fully elucidated. Our previous transcriptome analysis of porcine TLR8 (pTLR8) signaling suggested the immune checkpoint receptor TIM-3 as the potential regulator for pTLR8. Here we investigated TIM-3 in the regulation of pTLR8 signaling and its Anti-infection activity. Our results showed that porcine TIM-3 is upregulated by pTLR8 signaling and TIM-3 inhibits pTLR8 signaling activity in a negative feedback way. Accordingly, TIM-3 disturbs pTLR8 mediated anti-bacterial and anti-viral activity. Mechanistically, TIM-3 suppresses PI3K-AKT pathway by inhibiting the TLR8-PI3K p85 interaction and subsequent Akt phosphorylation which is essential for TLR8 signaling and Anti-infection activity. Therefore, our study reveals new insights into innate immune TLR8 signaling and its Anti-infection function.

Keywords

Anti-infections; Checkpoint TIM-3; Porcine; Regulator; Toll like receptor 8 (TLR8).

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