C-Fiber Degeneration Enhances Alveolar Macrophage-Mediated IFN-alpha/beta Response to Respiratory Syncytial Virus

作者全名："He, Yu; Li, Changgen; Wang, Zhili; Yang, Zhongying; Wei, Jianhua; Ren, Luo; Deng, Yu; Chen, Shiyi; Ye, Zhixu; Zang, Na; Liu, Enmei"

作者地址："[He, Yu; Li, Changgen; Wang, Zhili; Yang, Zhongying; Wei, Jianhua; Ren, Luo; Deng, Yu; Chen, Shiyi; Zang, Na; Liu, Enmei] Chongqing Med Univ, Childrens Hosp, Dept Resp Med, Chongqing, Peoples R China; [He, Yu; Li, Changgen; Wang, Zhili; Yang, Zhongying; Wei, Jianhua; Ren, Luo; Deng, Yu; Chen, Shiyi; Zang, Na; Liu, Enmei] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [He, Yu; Li, Changgen; Wang, Zhili; Yang, Zhongying; Wei, Jianhua; Ren, Luo; Deng, Yu; Chen, Shiyi; Zang, Na; Liu, Enmei] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [He, Yu; Li, Changgen; Wang, Zhili; Yang, Zhongying; Wei, Jianhua; Ren, Luo; Deng, Yu; Chen, Shiyi; Zang, Na; Liu, Enmei] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Ye, Zhixu] Guizhou Prov Peoples Hosp, Dept Cent Lab, Guizhou, Peoples R China"

通信作者："Zang, N; Liu, EM (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Resp Med, Chongqing, Peoples R China.; Zang, N; Liu, EM (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Zang, N; Liu, EM (通讯作者)，Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Zang, N; Liu, EM (通讯作者)，Chongqing Key Lab Pediat, Chongqing, Peoples R China."

来源：MICROBIOLOGY SPECTRUM

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000882843100001

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：alveolar macrophages; C fibers; respiratory syncytial virus; transient receptor potential vanilloid 1; vasoactive intestinal peptide

摘要："Stimulation of unmyelinated C fibers, the nociceptive sensory nerves, by noxious stimuli is able to initiate host responses. Host defensive responses against respiratory syncytial virus (RSV) infection rely on the induction of a robust alpha/beta interferon (IFN-alpha/beta) response, which acts to restrict viral production and promote antiviral immune responses. Alveolar macrophages (AMs) are the major source of IFN-alpha/beta upon RSV infection. Here, we found that C fibers are involved in host defense against RSV infection. Compared to the control mice post-RSV infection, degeneration and inhibition of C fibers by blockade of transient receptor potential vanilloid 1 (TRPV1) lowered viral replication and alleviated lung inflammation. Importantly, AMs were markedly elevated in C-fiber-degenerated (KCF) mice post-RSV infection, which was associated with higher IFN-alpha/beta secretion as measured in bronchoalveolar lavage fluid (BALF) samples. Degeneration of C fibers contributed to the production of vasoactive intestinal peptide (VIP), which modulated AM and IFN-alpha/beta levels to protect against RSV infection. Collectively, these findings revealed the key role of C fibers in regulating AM and IFN-alpha/beta responses against RSV infection via VIP, opening the possibility for new therapeutic strategies against RSV. IMPORTANCE Despite continuous advances in medicine, safe and effective drugs against RSV infection remain elusive. As such, host-RSV interactions and host-directed therapies require further research. Unmyelinated C fibers, the nociceptive sensory nerves, play an important role in regulating the host response to virus. In the present study, from the perspective of neuroimmune interactions, we clarified that C-fiber degeneration enhanced the AM-mediated IFN-alpha/beta response against RSV via VIP, providing potential therapeutic targets for the treatment of RSV infection."

基金机构："National Natural Science Foundation of China; Venture and Innovation Support Program for Chongqing's Overseas Returnees, China; [82070013]; [cx2018150]"

基金资助正文："ACKNOWLEDGMENTS We thank Fadi Xu from the Lovelace Respiratory Research Institute for writing-editing guidance on this paper. This study was supported by the National Natural Science Foundation of China (82070013) and Venture and Innovation Support Program for Chongqing's Overseas Returnees, China (cx2018150)."