Substance P receptor signaling contributes to host maladaptive responses during enteric bacterial infection

• 成果类型: Article
• 署名作者: Cremin, Michael; Ramirez, Valerie T.; Sanchez, Kristina; Tay, Emmy; Murray, Kaitlin; Brust-Mascher, Ingrid; Reardon, Colin
• 署名单位: University of California System; University of California Davis
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11518
• DOI: 10.1073/pnas.2415287122
• 发表日期: 2025-02-18
• 关键词: microvascular endothelial-cells; adhesion molecule-1; induced colitis; mouse skin; antagonist; expression; neurons; infiltration; inflammation; clearance

摘要

Immune responses in the intestine are intricately balanced to prevent pathogen entry without inducing immunopathology. The nervous system is well established to interface with the immune system to fine- tune immunity in various organ systems including the gastrointestinal tract. Specialized sensory neurons can detect bacteria, bacterial products, and the resulting inflammation, to coordinate the immune response in the gastrointestinal tract. These sensory neurons release peptide neurotransmitters such as Substance P (SP), to induce both neuronal signaling and localized responses in nonneuronal cells. With this in mind, we assessed the immunoregulatory roles of SP receptor signaling during enteric bacterial infection with the noninvasive pathogen Citrobacter rodentium. and prevented colonic crypt hyperplasia. Mice with SP receptor signaling blockade had significantly reduced inflammation and recruitment of T cells in the colon. Reduced reduce inflammation and prevent host- maladaptive responses without impinging upon