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Abstract
Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response against Mycobacterium tuberculosis (Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role during Mtb infection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellular Mtb and IL-17A and TGF-β immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-β that may be contributing to late fibrosis in TB lesions.
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1 University of Manchester, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); University of Manchester, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407)
2 Instituto Nacional de Ciencias Medicas y Nutricion “Salvador Zubiran”, Seccion de Patologia Experimental, Mexico City, Mexico (GRID:grid.416850.e) (ISNI:0000 0001 0698 4037)
3 Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Departamento de Inmunologia, Mexico City, Mexico (GRID:grid.9486.3) (ISNI:0000 0001 2159 0001)
4 Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico (GRID:grid.414757.4) (ISNI:0000 0004 0633 3412)
5 University of Manchester, Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); University of Manchester, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); University of Manchester, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407)