Background T cells cooperate with the intestinal microbiota to coordinate antimicrobial defense, but whether this crosstalk arose as an independent innovation in mammals or represents an evolutionarily conserved feature of vertebrate immunity remains unknown. Results Using the teleost Nile tilapia as a model, we demonstrate that both systemic and localized infection with Edwardsiella piscicida induce enteritis, correlated with robust intestinal T cell responses. Selective T cell depletion triggered excessive expression of proinflammatory cytokines, impaired mucosal architecture, and diminished host resistance to infection, underscoring the essential role of T cells in gut immunity. Strikingly, T cell depletion also caused profound alterations in gut microbial composition, characterized by a sharp decline in beneficial taxa such as Cetobacterium and the expansion of opportunistic pathogens including Klebsiella and Acinetobacter, indicating that T cells are required to maintain microbiome homeostasis. Conversely, broad-spectrum antibiotic eradication of the microbiota provoked hyperproliferation of intestinal T cells and barrier disruption, revealing reciprocal regulation between T cells and commensals. From the gut content, we isolated a C. somerae strain SH518, whose dietary supplementation for 6–8 weeks enhanced the activation, proliferation, and effector function of intestinal T cells, preserved mucosal homeostasis during E. piscicida challenge, and even boosted systemic T cell immunity in the spleen. Conclusions Collectively, these findings demonstrate that teleost T cells engage in bidirectional interactions with gut microbiota to orchestrate both antimicrobial defense and mucosal homeostasis. We therefore propose that T cell–microbiota cooperation represents an evolutionarily ancient strategy predates terrestrial adaptation, offering new insights into the coevolution of mucosal T cell immunity and microbiome. <MediaObject ID="MOESM2"> <VideoObject FileRef="MediaObjects/40168_2026_2370_MOESM2_ESM.mp4" VideoID="1PszfewxYJPE9JN18u8Y_f"> <Caption Language="En" xml:lang="en"> <CaptionContent> Video Abstract </CaptionContent> </Caption> </VideoObject> </MediaObject>

Gut T cell-microbiota crosstalk orchestrates antibacterial immunity and mucosal homeostasis in teleost

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2026年2月28日

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Ming Geng,
Yuying Zheng,
Shiqi Tang,
Zhichao Fang,
Tong Wang,
Kang Li,
Haokai Chen,
Jiansong Zhang,
Nannan Zhou,
Xiumei Wei,
Jialong Yang

摘要

Background

T cells cooperate with the intestinal microbiota to coordinate antimicrobial defense, but whether this crosstalk arose as an independent innovation in mammals or represents an evolutionarily conserved feature of vertebrate immunity remains unknown.

Results

Using the teleost Nile tilapia as a model, we demonstrate that both systemic and localized infection with Edwardsiella piscicida induce enteritis, correlated with robust intestinal T cell responses. Selective T cell depletion triggered excessive expression of proinflammatory cytokines, impaired mucosal architecture, and diminished host resistance to infection, underscoring the essential role of T cells in gut immunity. Strikingly, T cell depletion also caused profound alterations in gut microbial composition, characterized by a sharp decline in beneficial taxa such as Cetobacterium and the expansion of opportunistic pathogens including Klebsiella and Acinetobacter, indicating that T cells are required to maintain microbiome homeostasis. Conversely, broad-spectrum antibiotic eradication of the microbiota provoked hyperproliferation of intestinal T cells and barrier disruption, revealing reciprocal regulation between T cells and commensals. From the gut content, we isolated a C. somerae strain SH518, whose dietary supplementation for 6–8 weeks enhanced the activation, proliferation, and effector function of intestinal T cells, preserved mucosal homeostasis during E. piscicida challenge, and even boosted systemic T cell immunity in the spleen.

Conclusions

Collectively, these findings demonstrate that teleost T cells engage in bidirectional interactions with gut microbiota to orchestrate both antimicrobial defense and mucosal homeostasis. We therefore propose that T cell–microbiota cooperation represents an evolutionarily ancient strategy predates terrestrial adaptation, offering new insights into the coevolution of mucosal T cell immunity and microbiome.

Video Abstract