Nociceptive sensory neurons promote CD8 T cell responses to HSV-1 infection

Jessica Filtjens, Anais Roger, Linda Quatrini, Elisabeth Wieduwild, Jordi Gouilly, Guillaume Hoeffel, Rafaëlle Rossignol, Clara Daher, Guilhaume Debroas, Sandrine Henri, Claerwen M. Jones, Bernard Malissen, Laura K. Mackay, Aziz Moqrich, Francis R. Carbone and Sophie Ugolini ()
Additional contact information
Jessica Filtjens: Centre d’Immunologie de Marseille-Luminy
Anais Roger: Centre d’Immunologie de Marseille-Luminy
Linda Quatrini: Centre d’Immunologie de Marseille-Luminy
Elisabeth Wieduwild: Centre d’Immunologie de Marseille-Luminy
Jordi Gouilly: Centre d’Immunologie de Marseille-Luminy
Guillaume Hoeffel: Centre d’Immunologie de Marseille-Luminy
Rafaëlle Rossignol: Centre d’Immunologie de Marseille-Luminy
Clara Daher: Centre d’Immunologie de Marseille-Luminy
Guilhaume Debroas: Centre d’Immunologie de Marseille-Luminy
Sandrine Henri: Centre d’Immunologie de Marseille-Luminy
Claerwen M. Jones: The University of Melbourne at The Peter Doherty Institute for Infection and Immunity
Bernard Malissen: Centre d’Immunologie de Marseille-Luminy
Laura K. Mackay: The University of Melbourne at The Peter Doherty Institute for Infection and Immunity
Aziz Moqrich: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de
Francis R. Carbone: The University of Melbourne at The Peter Doherty Institute for Infection and Immunity
Sophie Ugolini: Centre d’Immunologie de Marseille-Luminy

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Host protection against cutaneous herpes simplex virus 1 (HSV-1) infection relies on the induction of a robust adaptive immune response. Here, we show that Nav1.8+ sensory neurons, which are involved in pain perception, control the magnitude of CD8 T cell priming and expansion in HSV-1-infected mice. The ablation of Nav1.8-expressing sensory neurons is associated with extensive skin lesions characterized by enhanced inflammatory cytokine and chemokine production. Mechanistically, Nav1.8+ sensory neurons are required for the downregulation of neutrophil infiltration in the skin after viral clearance to limit the severity of tissue damage and restore skin homeostasis, as well as for eliciting robust CD8 T cell priming in skin-draining lymph nodes by controlling dendritic cell responses. Collectively, our data reveal an important role for the sensory nervous system in regulating both innate and adaptive immune responses to viral infection, thereby opening up possibilities for new therapeutic strategies.

Date: 2021
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DOI: 10.1038/s41467-021-22841-6

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