Identification of a unique TUBB3+ cell population in the tuberculosis granuloma

Sarah Monard; Arnaud Métais; Maxime Pingret; Caroline Buscail; Maxime Caouaille; Marion Faucher; Serge Mazères; Renaud Poincloux; Yoann Rombouts; Bruce S. Klein; Marcel Wüthrich; Francisco Javier Salguero; Simon O Clark; Xavier Montagutelli; Etienne Simon‐Lorière; Jean‐Michel Molina; Nathalie De Castro; Nicolas Gaudenzio; Sergo A. Vashakidze; Claire Magnon; Cristina Vilaplana; Geanncarlo Lugo‐Villarino; Christel Vérollet; Olivier Neyrolles

doi:10.1101/2025.03.04.641465

ImmunologybioRxivMar 4, 2025

Preprint

Identification of a unique TUBB3+ cell population in the tuberculosis granuloma

Sarah Monard iD, Arnaud Métais iD, Maxime Pingret, Caroline Buscail, Maxime Caouaille iD, Marion Faucher iD, Serge Mazères iD, Renaud Poincloux iD, Yoann Rombouts iD, Bruce S. Klein iD, Marcel Wüthrich iD, Francisco Javier Salguero iD, Simon O Clark iD, Xavier Montagutelli iD, Etienne Simon‐Lorière iD, Jean‐Michel Molina iD, Nathalie De Castro iD, Nicolas Gaudenzio iD, Sergo A. Vashakidze iD, Claire Magnon iD, Cristina Vilaplana iD, Geanncarlo Lugo‐Villarino iD, Christel Vérollet iD, Olivier Neyrolles iD

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading cause of mortality worldwide. Granulomas, hallmark structures of TB in the lungs and other infected tissues, are critical sites of host-pathogen interactions, yet their full cellular composition is not completely understood. Here, we identify a previously unrecognized {beta}3-tubulin (TUBB3)-positive cell population within TB granulomas in mice, guinea pigs, non-human primates, and TB patients. TUBB3 is a well-established pan-neuronal marker, yet these TUBB3+ cells are distinct from typical pulmonary resident cells and leukocytes. They exhibit a branched, elongated morphology, which is suggestive of neuron-like features. Intriguingly, their appearance is independent of adaptive immunity and is also observed in viral and fungal infections, but not in asthma. Our findings suggest the existence of a neuro-immune component within granulomas that may influence TB pathogenesis. Further investigation into the origin, function, and signaling pathways of these TUBB3+ cells is required to clarify their identity and potential role in host defense, which could reveal novel therapeutic targets for TB and other pulmonary infections.

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