Differential mast cell numbers and characteristics in human tuberculosis pulmonary lesions

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.

Uncovering the Mast Cell Response to Mycobacterium tuberculosis

“…When studying more severe pulmonary TB among patients admitted to the intensive care units, it was observed that these patients have an increased MCs in lung tissue ( 78 ). In fact, a recent study analyzed fibrotic tissue from post-mortem lung tissue microarrays from individuals with pulmonary TB and healthy control subjects ( 79 ). They demonstrated that MCs were localized at pneumonic areas, in the granuloma periphery and particularly abundant.…”

Bacillus Calmette–Guérin-Induced Human Mast Cell Activation Relies on IL-33 Priming

“…Interestingly, IL-33 pre-treatment in hMCs also increased IL-13 secretion upon BCG infection and 19-kDa stimulation. IL-13 contributes to the process of lung fibrosis in human TB [ 42 ], since MCs are abundant in fibrotic sites of human pulmonary TB-associated lesions [ 43 ]. Therefore, in humans, IL-33 may exacerbate the fibrotic process mediated by IL-13 in a MC-dependent manner.…”

Pyogranulomatous dermatitis withEnterococcus faecalisin a spotted seal (Phoca larga)

“…Upon bacterial exposure, they are recruited and release a wide variety of cytokines and chemokines to have immunoregulatory functions and suppress chronic inflammation, including IL‐2, IL‐10, IL‐17, IL‐18 and TGF‐β, by degranulation or the canonical secretory pathway (Melissa et al., 2016 ; Zhang & Kurashima, 2021 ). Furthermore, mast cells may contribute to late fibrosis in infectious granuloma by proteases and TGF‐β (Garcia‐Rodriguez et al., 2021 ). Connective tissue proliferation is a common sign of chronic inflammation and it can limit the expansion of infection, such as forming a fibrous envelope (Zachary, 2017 ).…”