Cold- blooded vertebrate utilizes behavioral fever to alleviate T cell apoptosis and optimize antimicrobial immunity

• 成果类型: Article
• 署名作者: Gao, Haiyou; Wei, Xiumei; Li, Kang; Cao, Yi; Rao, Wenzhuo; Zhang, Jiansong; Wang, Ding; Yang, Jialong
• 署名单位: East China Normal University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11303
• DOI: 10.1073/pnas.2408969121
• 发表日期: 2024-12-24
• 关键词: thermal regulation; temperature; differentiation; stimulation; PATHWAY; kinase; hsp70

摘要

Fever confers significant survival benefits on endotherms by optimizing both innate and adaptive immunity. Ectotherms achieve thermoregulation using behavioral strategies, but existing evidence supports its enhancement effect on innate immunity only. Therefore, it remains unknown whether the coordination between fever and adaptive immunity was independently acquired by endotherms or instead represents a gradually evolved function common to vertebrates. In the present study, we reported that Nile tilapia developed behavioral fever to enhance the immune response against Edwardsiella piscicida infection. Behavioral fever lasted five days, and the immune potential was optimized at 4 to 6 d post infection, indicating a potential correlation between fever events and T cell immunity. Further investigation suggested that fever did not affect T cell activation or proliferation but improved the ability of T cells to produce IFN-gamma and Granzyme B and enhanced cytotoxicity, thereby eliminating the infection more effectively. Notably, we identified an advantage conferred by fever during infection: alleviation of T cell apoptosis to maintain a considerable T cell pool. Mechanistically, fever induced the expression of HSP70, which in turn entered the nucleus and bound to and promoted the phosphorylation of ERK1/2, thereby inhibiting the cleavage of caspase- 8/caspase- 3 and preventing T cell apoptosis. Our findings elucidate the detailed mechanism by which behavioral fever optimizes T cell immunity in a cold- blooded vertebrate and propose that integrating fever with adaptive immunity to gain survival advantages is an ancient strategy acquired before the emergence of tetrapod.