Linking severe traumatic brain injury to pulmonary Infections: Translocation of intestinal bacteria mediated by nociceptor neurons

• Published in: Brain, behavior, and immunity behavior, and immunity, 2024-11, Vol.122, p.604-616
• Main Authors: You, Xinyu, Niu, Lin, Song, Xuejiao, Fu, Jiafeng, Miao, Yulu, Diao, Fengyin, Wu, Chongming, Zhuang, Pengwei, Zhang, Yanjun
• Format: Article
• Language: English
• Subjects: Bacterial translocation; CGRP; Microfold cells; Pulmonary infection; Severe traumatic brain injury; TRPV1 nociceptor
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2024.08.041

[Display omitted] •Pulmonary infections following severe traumatic brain injury originate from the translocation of the host’s gut-resident bacteria.•TRPV1+ nociceptor in the dorsal root ganglion play a protective role against gut microbiota translocation.•The regulation of gut microbiota translocation by TRPV1+ nociceptors is contingent upon the delicate homeostasis of microfold cells. The prevalence of bacterial infections significantly increases among patients with severe traumatic brain injury (STBI), leading to a notable rise in mortality rates. While immune dysfunctions are linked to the incidence of pneumonia, our observations indicate that endogenous pathogens manifest in the lungs post-STBI due to the migration of gut commensal bacteria. This translocation involves gut-innervating nociceptor sensory neurons, which are crucial for host defense. Following STBI, the expression of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons significantly decreases, despite an initial brief increase. The timing of TRPV1 defects coincides with the occurrence of pulmonary infections post-STBI. This alteration in TRPV1+ neurons diminishes their ability to signal bacterial injuries, weakens defense mechanisms against intestinal bacteria, and increases susceptibility to pulmonary infections via bacterial translocation. Experimental evidence demonstrates that pulmonary infections can be successfully replicated through the chemical ablation and gene interference of TRPV1+ nociceptors, and that these infections can be mitigated by TRPV1 activation, thereby confirming the crucial role of nociceptor neurons in controlling intestinal bacterial migration. Furthermore, TRPV1+ nociceptors regulate the immune response of microfold cells by releasing calcitonin gene-related peptide (CGRP), thereby influencing the translocation of gut bacteria to the lungs. Our study elucidates how changes in nociceptive neurons post-STBI impact intestinal pathogen defense. This new understanding of endogenous risk factors within STBI pathology offers novel insights for preventing and treating pulmonary infections.