tetano
Editor, Senior Moderator
Sci Immunol
. 2025 Aug;10(110):eads6243.
doi: 10.1126/sciimmunol.ads6243. Epub 2025 Aug 1. Vagal TRPV1[SUP]+[/SUP] sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics
Nicole Almanzar[SUP] 1 2 [/SUP], Daping Yang[SUP] 1 3 [/SUP], Jingya Xia[SUP] 1 [/SUP], Swalpa Udit[SUP] 1 [/SUP], Prabhu Joshi[SUP] 4 [/SUP], Sandeep Adhikari[SUP] 4 [/SUP], Daisy A Hoagland[SUP] 1 5 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Camille Khairallah[SUP] 6 [/SUP], Tomas Huerta[SUP] 1 [/SUP], Antonia Wallrapp[SUP] 1 [/SUP], Benjamin D Umans[SUP] 7 [/SUP], Nicole Sarden[SUP] 8 [/SUP], Ozge Erdogan[SUP] 1 9 [/SUP], Nadia Baalbaki[SUP] 1 [/SUP], Jiawei Hou[SUP] 3 [/SUP], Anna Beekmayer-Dhillon[SUP] 1 [/SUP], Juhyun Lee[SUP] 1 [/SUP], Kimberly A Meerschaert[SUP] 1 [/SUP], Stephen D Liberles[SUP] 7 [/SUP], Ruth A Franklin[SUP] 1 5 10 [/SUP], Bryan G Yipp[SUP] 8 [/SUP], Kamal M Khanna[SUP] 6 [/SUP], Pankaj Baral[SUP] 1 4 [/SUP], Adam L Haber[SUP] 2 [/SUP], Isaac M Chiu[SUP] 1 [/SUP]
Affiliations
Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1[SUP]+[/SUP] nociceptive sensory neurons are known to mediate defenses against harmful agents, including pathogens, their function in lung antiviral defenses remains unclear. Our study demonstrates that both systemic and vagal-specific ablation of TRPV1[SUP]+[/SUP] nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1[SUP]+[/SUP] neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1[SUP]+[/SUP] neurons altered the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in myeloid cells and an imbalance in distinct neutrophil subpopulations in the absence of nociceptors. Furthermore, antibody-mediated depletion of myeloid cells during IAV infection substantially improved survival after nociceptor ablation, underscoring the role of TRPV1[SUP]+[/SUP] neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.
. 2025 Aug;10(110):eads6243.
doi: 10.1126/sciimmunol.ads6243. Epub 2025 Aug 1. Vagal TRPV1[SUP]+[/SUP] sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics
Nicole Almanzar[SUP] 1 2 [/SUP], Daping Yang[SUP] 1 3 [/SUP], Jingya Xia[SUP] 1 [/SUP], Swalpa Udit[SUP] 1 [/SUP], Prabhu Joshi[SUP] 4 [/SUP], Sandeep Adhikari[SUP] 4 [/SUP], Daisy A Hoagland[SUP] 1 5 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Camille Khairallah[SUP] 6 [/SUP], Tomas Huerta[SUP] 1 [/SUP], Antonia Wallrapp[SUP] 1 [/SUP], Benjamin D Umans[SUP] 7 [/SUP], Nicole Sarden[SUP] 8 [/SUP], Ozge Erdogan[SUP] 1 9 [/SUP], Nadia Baalbaki[SUP] 1 [/SUP], Jiawei Hou[SUP] 3 [/SUP], Anna Beekmayer-Dhillon[SUP] 1 [/SUP], Juhyun Lee[SUP] 1 [/SUP], Kimberly A Meerschaert[SUP] 1 [/SUP], Stephen D Liberles[SUP] 7 [/SUP], Ruth A Franklin[SUP] 1 5 10 [/SUP], Bryan G Yipp[SUP] 8 [/SUP], Kamal M Khanna[SUP] 6 [/SUP], Pankaj Baral[SUP] 1 4 [/SUP], Adam L Haber[SUP] 2 [/SUP], Isaac M Chiu[SUP] 1 [/SUP]
Affiliations
- PMID: 40749036
- DOI: 10.1126/sciimmunol.ads6243
Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1[SUP]+[/SUP] nociceptive sensory neurons are known to mediate defenses against harmful agents, including pathogens, their function in lung antiviral defenses remains unclear. Our study demonstrates that both systemic and vagal-specific ablation of TRPV1[SUP]+[/SUP] nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1[SUP]+[/SUP] neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1[SUP]+[/SUP] neurons altered the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in myeloid cells and an imbalance in distinct neutrophil subpopulations in the absence of nociceptors. Furthermore, antibody-mediated depletion of myeloid cells during IAV infection substantially improved survival after nociceptor ablation, underscoring the role of TRPV1[SUP]+[/SUP] neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.