<p>Antimicrobial peptides (AMPs) are essential components of the innate immune system in animals, playing crucial roles in defending against microbial infections. Hydrogen sulfide (H<sub>2</sub>S), a vital gasotransmitter, is involved in regulating a wide array of physiological functions. However, the role of H₂S in the anti-infective actions of AMPs remains poorly understood. Here, we demonstrate the crucial role of H<sub>2</sub>S in mediating the anti-infective functions of AMPs across diverse animal species. LL-37/CRAMP, the human cathelicidin family AMP and its mouse homolog, induce H<sub>2</sub>S production predominantly through 3-mercaptopyruvate sulfurtransferase (3MST) in <i>Escherichia coli</i> and <i>Clostridium perfringens</i>. The generated H₂S further participates in reactive oxygen species (ROS) accumulation, leading to bacterial death by oxidative damage. Additionally, LL-37 activates the Akt signaling pathway, upregulating cystathionine γ-lyase (CSE) expression to generate H<sub>2</sub>S in macrophages. This process plays a potential role in facilitating the immunomodulatory activity of LL-37/CRAMP and we confirmed that H<sub>2</sub>S is involved in their in vivo anti-infective activity of LL-37. Moreover, besides LL-37/CRAMP, we reveal that AMPs from various animal species also induce H<sub>2</sub>S production in bacteria and macrophages. Overall, our findings highlight a previously unrecognized role of H<sub>2</sub>S in AMP anti-infective function, which is ubiquitous across AMPs from different animals.</p>

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The potential role of H2S in the anti-infective function of antimicrobial peptides

  • Xu Wang,
  • Shuangyu Li,
  • Wenzhuang Shi,
  • Beiru Xue,
  • Xu Wang,
  • Miao Liu,
  • Binjuan Lu,
  • Zhouye Xu,
  • Ye Gao,
  • Jiachang Liu,
  • Xingyue Ji,
  • Jia-Tang Li,
  • Yipeng Wang

摘要

Antimicrobial peptides (AMPs) are essential components of the innate immune system in animals, playing crucial roles in defending against microbial infections. Hydrogen sulfide (H2S), a vital gasotransmitter, is involved in regulating a wide array of physiological functions. However, the role of H₂S in the anti-infective actions of AMPs remains poorly understood. Here, we demonstrate the crucial role of H2S in mediating the anti-infective functions of AMPs across diverse animal species. LL-37/CRAMP, the human cathelicidin family AMP and its mouse homolog, induce H2S production predominantly through 3-mercaptopyruvate sulfurtransferase (3MST) in Escherichia coli and Clostridium perfringens. The generated H₂S further participates in reactive oxygen species (ROS) accumulation, leading to bacterial death by oxidative damage. Additionally, LL-37 activates the Akt signaling pathway, upregulating cystathionine γ-lyase (CSE) expression to generate H2S in macrophages. This process plays a potential role in facilitating the immunomodulatory activity of LL-37/CRAMP and we confirmed that H2S is involved in their in vivo anti-infective activity of LL-37. Moreover, besides LL-37/CRAMP, we reveal that AMPs from various animal species also induce H2S production in bacteria and macrophages. Overall, our findings highlight a previously unrecognized role of H2S in AMP anti-infective function, which is ubiquitous across AMPs from different animals.