Immunity to the Dual Threat of Silica Exposure and Mycobacterium tuberculosis

Abstract

Exposure to silica and the consequent development of silicosis are well-known health problems in countries with mining and other dust producing industries. Apart from its direct fibrotic effect on lung tissue, chronic and immunomodulatory character of silica causes susceptibility to tuberculosis (TB) leading to a significantly higher TB incidence in silica-exposed populations. The presence of silica particles in the lung and silicosis may facilitate initiation of tuberculous infection and progression to active TB, and exacerbate the course and outcome of TB, including prognosis and survival. However, the exact mechanisms of the involvement of silica in the pathological processes during mycobacterial infection are not yet fully understood. In this review, we focus on the host's immunological response to both silica and Mycobacterium tuberculosis, on agents of innate and adaptive immunity, and particularly on silica-induced immunological modifications in co-exposure that influence disease pathogenesis. We review what is known about the impact of silica and Mycobacterium tuberculosis or their co-exposure on the host's immune system, especially an impact that goes beyond an exclusive focus on macrophages as the first line of the defense. In both silicosis and TB, acquired immunity plays a major role in the restriction and/or elimination of pathogenic agents. Further research is needed to determine the effects of silica in adaptive immunity and in the pathogenesis of TB.

Mini-review: Silico-tuberculosis

“…In rat models, defence against Mycobacterium tuberculosis becomes poorer as silicosis progresses [25] . However, silica-induced Th1 responses, with TNF-alpha and IFN-gamma production, should contribute to resistance to, or elimination of, Mycobacterium tuberculosis [26] . The pathophysiological mechanisms are still incompletely identified.…”

“…Additional studies are clearly needed on the pathophysiology of silico-tuberculosis. In particular, no research has been done on dendritic cells, neutrophils, NK cells, B cells, and only scanted and contradictory data are available on T cells [26] .…”

Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity

“…Fine particulate air pollutants have been associated with tuberculosis incidence and outcome (Popovic et al, 2019). However, the underlying mechanisms by which patients exposed to silica become predisposed to the development of severe tuberculosis are poorly understood (Kone cný et al, 2019). Inhaled crystalline silica affects immune and non-immune cell types, resulting in responses ranging from inflammation to oxidative stress and cell death (Joshi and Knecht, 2013;Porter et al, 2004Porter et al, , 2006.…”

Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate ofMycobacterium tuberculosisin patients with multidrug-resistant tuberculosis in Tanzania

“…We have shown that patients with TB/silicosis had slower M. tuberculosis elimination rates by TB-MBLA compared to those with TB and without silicosis. This slow rate of elimination could partially be attributed to the underlying pulmonary pathophysiology which can include progressive massive fibrosis [28,29] , and anatomically, a blunted local host immune response to M. tuberculosis infection [28] . We observed a similarly slower rate of M. tuberculosis elimination among patients with RR/MDR-TB who had high initial bacterial load, which supplements previous studies of TB-MBLA kinetics from patients with drug sensitive TB [6,8,19] .…”