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

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 β3-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.