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

Monard, S.; Metais, A.; Pingret, M.; Buscail, C.; Caouaille, M.; Faucher, M.; Mazeres, S.; Poincloux, R.; Rombouts, Y.; Klein, B. S.; Wuethrich, M.; Salguero, F. J.; Clark, S. O.; Montagutelli, X.; Simon-Loriere, E.; Molina, J.-M.; De Castro, N.; Gaudenzio, N.; Vashakidze, S.; Magnon, C.; Vilaplana, C.; Lugo-Villarino, G.; Verollet, C.; Neyrolles, O.

doi:10.1101/2025.03.04.641465

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bioRxiv · 10.1101/2025.03.04.641465

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

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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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Monard, S., Metais, A., Pingret, M., Buscail, C., Caouaille, M., Faucher, M., Mazeres, S., Poincloux, R., Rombouts, Y., Klein, B. S., Wuethrich, M., Salguero, F. J., Clark, S. O., Montagutelli, X., Simon-Loriere, E., Molina, J.-M., De Castro, N., Gaudenzio, N., Vashakidze, S., Magnon, C., Vilaplana, C., Lugo-Villarino, G., Verollet, C., Neyrolles, O.. 2025-03-10. Identification of a unique TUBB3+ cell population in the tuberculosis granuloma. https://doi.org/10.1101/2025.03.04.641465

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