Vagal TRPV1<sup>+</sup> sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics.

Overview

Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1⁺ 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⁺ nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1⁺ neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1⁺ 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⁺ neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.