2. Academic Validation
  3. Staphylococcus Aureus Tames Nociceptive Neurons to Suppress Synovial Macrophage Responses for Sustained Infection in Septic Arthritis

Staphylococcus Aureus Tames Nociceptive Neurons to Suppress Synovial Macrophage Responses for Sustained Infection in Septic Arthritis

  • Adv Sci (Weinh). 2025 Feb 17:e2409251. doi: 10.1002/advs.202409251.
Xinyu Fang 1 2 3,  Yang Chen 1 2 3,  Haiqi Ding 1 2 3,  Changyu Huang 1 2 3,  Hongxin Hu 1 2 3,  Chaofan Zhang 1 2 3,  Yunzhi Lin 4,  Qijin Wang 1 2 3,  Xueni Hu 5,  Yiming Lin 1 2 3,  Yongfa Chen 1 2 3,  Nanxin Zhang 1 2 3,  Xuhui Yuan 1 2 3,  Ying Huang 1 2 3,  Wenbo Li 1 2 3,  Susheng Niu 6,  Jianhua Lin 1 2 3,  Bin Yang 5,  Tifei Yuan 7 8,  Wenming Zhang 1 2 3
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350000, China.
  • 2 Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, China.
  • 3 Fujian Provincial Institute of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350000, China.
  • 4 Department of Stomatology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350000, China.
  • 5 Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, China.
  • 6 Key Laboratory of Orthopedics & Traumatology of Traditional Chinese Medicine and Rehabilitation Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou, 350000, China.
  • 7 Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.
  • 8 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226019, China.
PMID: 39960341 DOI: 10.1002/advs.202409251
Abstract

The interaction between the nervous system and immune system during chronic Bacterial infection remains unclear. Here, it is reported that Staphylococcus aureus (S. aureus) Infection induces Calcitonin gene-related peptide (CGRP) secretion from intra-articular transient receptor potential cation channel subfamily V member 1 positive (TRPV1+) nociceptive nerves through its pore-forming toxin (PFT) α-hemolysin. The released CGRP then inhibits the production of chemotactic cytokines by CX3CR1+ tissue-resident synovial lining macrophages via receptor activity modifying protein 1 (RAMP1) receptors at the onset of septic arthritis. During the subsequent chronic course of Infection, the continuous release of CGRP triggered by pain has a lasting effect on the antimicrobial capabilities of macrophages, thereby promoting Bacterial survival and joint damage. This evidence suggests a critical role for neuroimmune regulation in S. aureus-induced chronic septic arthritis. CGRP Receptor antagonism may reduce joint destruction, thus providing a new option for treating bone and joint infections.

Keywords

Staphylococcus aureus; calcitonin gene‐related peptide; chronic septic arthritis; macrophages; nociceptive neuron.

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