4.
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
5.
Texas Biomedical Research Institute
Description
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), infects approximately one-fourth of the world's population. We reported an increased accumulation of mast cells (MCs) in the lungs of macaques with active pulmonary TB (PTB), compared with those with latent TB infection (LTBI). MCs respond in vitro to Mtb exposure via degranulation and by inducing proinflammatory cytokines. In the current study, we demonstrate an increased production of chymase by MCs in granulomas of humans and macaques with PTB. Single-cell (sc) RNA sequencing analysis revealed distinct MC transcriptional programs between LTBI and PTB, with PTB-associated MCs enriched in interferon gamma, oxidative phosphorylation, and MYC signaling. In a mouse model, MC deficiency led to improved control of Mtb infection that coincided with reduced accumulation of lung myeloid cells and diminished lung inflammation at chronic stages of infection. Airway transfer of MCs into wild-type Mtb-infected mice showed increased neutrophils, decreased recruited macrophages, and elevated Mtb dissemination to the spleen. Together, these findings highlight MCs as active drivers of TB pathogenesis and potential targets for host-directed therapies for TB.
Data availability
We did not generate new datasets and have used publicly available datasets mentioned in the section below.
The following previously published data sets were used:
Esaulova E Das S Singh DK Choreño-Parra JA Swain A Arthur L Rangel-Moreno J Ahmed M Bucsan A Moodley C Mehra S García-Latorre E Zuniga J Atkinson J Kaushal D Artyomov MN Khader SA (2021) NCBI Gene Expression Omnibus ID GSE149758. Defining the tuberculosis lung landscape during disease and latency using single cell technologies.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149758
Gideon HP Hughes TK Tzouanas CN Wadsworth MH (2022) NCBI Gene Expression Omnibus ID GSE200151. Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE200151
