STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Veterinary Research Année : 2024

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling

Zhen-Zhen Liu
  • Fonction : Auteur
Cheng-Kai Zhou
  • Fonction : Auteur
Xiao-Qi Lin
  • Fonction : Auteur
Yu Gao
  • Fonction : Auteur
Xue-Yue Luo
  • Fonction : Auteur
Jia-Bao Zhang
  • Fonction : Auteur
Qi Yin
  • Fonction : Auteur
Liang Zhang
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Jian-Gang Zhang
  • Fonction : Auteur
Xin An
  • Fonction : Auteur
Wei Chen
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Yong-Jun Yang
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Résumé

AbstractClostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING‑deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.
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Origine : Publication financée par une institution

Dates et versions

hal-04553980 , version 1 (22-04-2024)

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Zhen-Zhen Liu, Cheng-Kai Zhou, Xiao-Qi Lin, Yu Gao, Xue-Yue Luo, et al.. STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling. Veterinary Research, 2024, 55 (1), pp.52. ⟨10.1186/s13567-024-01301-1⟩. ⟨hal-04553980⟩

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