
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.04.611333
preprint
1
Article
Mast cells promote pathology and susceptibility in tuberculosis
Gupta Ananya
Taneja Vibha
Rangel Moreno Javier
Abhimanyu
Ahmed Mushtaq
Naqvi Nilofer
Chauhan Kuldeep S.
de León Daniela Trejo-Ponce
Ramírez-Martínez Gustavo
Jiménez-Alvarez Luis
Luna-Rivero Cesar
Zuniga Joaquin
Kaushal Deepak
Khader Shabaana A. http://orcid.org/0000-0002-9545-4982

09 9 2024
2024.09.04.611333https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.09.04.611333
nihpp-2024.09.04.611333.pdf
Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis ( Mtb ), infects approximately one-fourth of the world’s population. While most infected individuals are asymptomatic, latent TB infection (LTBI) can progress to cause pulmonary TB (PTB). We recently reported an increased accumulation of mast cells (MCs) in lungs of macaques with PTB, compared with LTBI in macaques. MCs respond in vitro to Mtb exposure via degranulation and by inducing proinflammatory cytokines. In the current study, we show the dominant production of chymase by MCs in granulomas of humans and macaques with PTB. Using scRNA seq analysis, we show that MCs found in LTBI and healthy lungs in macaques are enriched in genes involved in tumor necrosis factor alpha, cholesterol and transforming growth factor beta signaling. In contrast, MCs clusters found in PTB express transcriptional signatures associated with interferon gamma, oxidative phosphorylation, and MYC signaling. Additionally, MC deficiency in the mouse model showed improved control of Mtb infection that coincided with reduced accumulation of lung myeloid cells and diminished inflammation at chronic stages. Thus, these collective results provide novel evidence for the pathological contribution of MCs during Mtb infection and may represent a novel target for host directive therapy for TB.
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pmc
