Neuro-TB

FRAMEWORK

• Context: Emergent themes on lung micro-environments and macrophage biology

• Duration: Oct 2020 – Present.

• Status: Ongoing.

• Role: Principal Investigator.

• Co-Principal Investigator: Dr. Christel Vérollet, DR2/Inserm.

• Funding:

  • 2023 — 2024. AO 2023-2 CSS11, Role as Work Package Manager.

Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS)  

“Characterization of Novel Pulmonary Neuron-Like Cells in TB Granulomas.”

• Personnel participating in this project:

  • • Dr. Geanncarlo Lugo-Villarino, DR2/CNRS

    • Dr. Olivier Neyrolles, DRCE/CNRS

    • Sarah Monard, PhD candidate (2021-2025)

• Collaboration: IPBS/CNRS, Toulouse

  • • Partner Team: Dr. Christel Vérollet and Renaud Poincloux

    • Key Personnel:

      • • • Dr. Christel Vérollet, DR2/Inserm

          • Dr. Arnaud Metais, Research Engineer (CNRS)

SUMMARY

In this project, my PhD student, Sarah Monard, investigated whether infection-induced remodeling of the pulmonary nervous system contributes to granuloma architecture during Mtb infection. Using immunohistology, tissue clearing, and comparative analyses across multiple host species, we identified the emergence of a previously unrecognized population of β3-tubulin (TUBB3)-positive cells within inflamed lung parenchyma. While TUBB3 is classically associated with neuronal lineage, these cells were distinct from the TUBB3⁺axons normally located in peribronchial regions of the healthy lung. Instead, infection induced the appearance of elongated TUBB3⁺cells within granulomas and inducible bronchus-associated lymphoid tissue (iBALT), where they localized in close proximity to macrophages and T cells. This phenomenon was conserved across multiple experimental models, including mice, guinea pigs, and non-human primates, as well as in human TB lesions, indicating that the remodeling of TUBB3⁺structures is a conserved feature of pulmonary TB.

SIGNIFICANCE

This study uncovers an unexpected TUBB3⁺stromal component associated with TB granulomas, revealing that pulmonary infection is accompanied by remodeling of neural-associated elements within inflamed lung tissue. By identifying TUBB3⁺cells positioned at the interface of immune infiltrates, this work establishes the conceptual foundation for our current research program investigating neuro–immune niches and stromal regulation of immunity in the infected lung. These results are available as a preprint on BioRxiv 2025, with Sarah as the first author, Dr. Neyrolles, Dr. Vérollet, and me as the last authors (Monard et al., bioRxiv preprint, 2025).