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Peer-reviewedCC BY-NC-NDCellular and molecular life sciences : CMLS

Bacterial stimulation triggers IRF7-mediated IFN-λ production in hepatocytes to attenuate sepsis

  • Wei Ma1
  • Junjie Shu1
  • Wanqi Tang1
  • Haoru Liu1
  • Hao Zhang1
  • Xue Yang1
  • Qiangguo Gao2
  • Huaping Liang1
  • Xia Yang1
  1. 1Chongqing, 400042 China
  2. 2Chongqing, 400038 China
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Abstract

Interferon lambda (IFN-λ) is produced early by hematopoietic or epithelial cells and acts as a primary mediator of frontline antiviral defense without inducing inflammatory responses. However, whether hepatocytes, rather than immune cells, can secrete IFN-λs to protect against bacterial infection remains unestablished. Here, we demonstrate that hepatocytes secrete IFN-λs in response to bacterial stimulation both in vivo and in vitro, and that this secreted IFN-λs directly inhibits bacterial proliferation. Mechanistically, during in vitro bacterial infection, the upregulation and activation of the transcription factor IRF7 drive type III interferon (IFN-λ) production in hepatocytes through a cascading TLR4 signaling pathway, rather than via RIG-I or MDA5. Importantly, pretreatment with IFN-λs, through interaction with IFNLR1 in hepatocytes, increases the number of dead bacteria, improves systemic outcomes, and enhances survival in septic mice. Furthermore, sepsis patients show increased expression levels of IRF7, IFN-λ2, and IFN-λ3. These findings reveal that IFN-λs function as active mediators against bacterial infection, eliciting a unique antibacterial response to eliminate bacteria. This work further suggests that enhancing IFN-λs production in hepatocytes could serve as a potential therapeutic strategy for sepsis.

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Cite

BibTeXRIS
BibTeX
@article{ma2026bacterial,
  title = {{Bacterial stimulation triggers IRF7-mediated IFN-λ production in hepatocytes to attenuate sepsis}},
  author = {Wei Ma and Junjie Shu and Wanqi Tang and Haoru Liu and Hao Zhang and Xue Yang and Qiangguo Gao and Huaping Liang and Xia Yang},
  journal = {Cellular and molecular life sciences : CMLS},
  year = {2026},
  month = jul,
  doi = {10.1007/s00018-026-06351-6},
  url = {https://europepmc.org/article/PMC/PMC13691052},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Bacterial stimulation triggers IRF7-mediated IFN-λ production in hepatocytes to attenuate sepsis
AU  - Wei Ma
AU  - Junjie Shu
AU  - Wanqi Tang
AU  - Haoru Liu
AU  - Hao Zhang
AU  - Xue Yang
AU  - Qiangguo Gao
AU  - Huaping Liang
AU  - Xia Yang
PY  - 2026
DA  - 2026/07/01
JO  - Cellular and molecular life sciences : CMLS
DO  - 10.1007/s00018-026-06351-6
UR  - https://europepmc.org/article/PMC/PMC13691052
AB  - Interferon lambda (IFN-λ) is produced early by hematopoietic or epithelial cells and acts as a primary mediator of frontline antiviral defense without inducing inflammatory responses. However, whether hepatocytes, rather than immune cells, can secrete IFN-λs to protect against bacterial infection remains unestablished. Here, we demonstrate that hepatocytes secrete IFN-λs in response to bacterial stimulation both in vivo and in vitro, and that this secreted IFN-λs directly inhibits bacterial proliferation. Mechanistically, during in vitro bacterial infection, the upregulation and activation of the transcription factor IRF7 drive type III interferon (IFN-λ) production in hepatocytes through a cascading TLR4 signaling pathway, rather than via RIG-I or MDA5. Importantly, pretreatment with IFN-λs, through interaction with IFNLR1 in hepatocytes, increases the number of dead bacteria, improves systemic outcomes, and enhances survival in septic mice. Furthermore, sepsis patients show increased expression levels of IRF7, IFN-λ2, and IFN-λ3. These findings reveal that IFN-λs function as active mediators against bacterial infection, eliciting a unique antibacterial response to eliminate bacteria. This work further suggests that enhancing IFN-λs production in hepatocytes could serve as a potential therapeutic strategy for sepsis.
SN  - 1420-682X
SN  - 1420-9071
ER  -