Advances in understanding the role of NLRP3 inflammasome-mediated macrophage pyroptosis in the pathogenesis of silicosis

Silicosis is an occupational lung disease with a well-defined etiology but a complex pathogenesis. In recent years, increasing evidence has revealed that macrophage pyroptosis plays a pivotal role in the initiation and progression of silicosis. The Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a key regulator of innate immune responses, is critically involved in macrophage pyroptosis. This review provides a comprehensive overview of the mechanisms by which NLRP3 inflammasome–mediated macrophage pyroptosis contributes to the development of silicosis. First, we summarize the fundamental concepts of the NLRP3 inflammasome and macrophage pyroptosis, as well as their molecular interactions. We then focus on how silica particles activate the NLRP3 inflammasome in macrophages, leading to caspase activation, gasdermin-mediated membrane pore formation, and the release of pro-inflammatory cytokines and damage-associated molecular patterns, thereby amplifying pulmonary inflammation and promoting interstitial fibrosis. In addition, dysbiosis of the lung microbiota is frequently observed in patients with silicosis, and emerging evidence suggests that microbial imbalance may further exacerbate disease progression by enhancing inflammasome activation and macrophage pyroptotic signaling. By integrating these interconnected mechanisms, this review aims to provide new theoretical insights and research directions for the prevention, diagnosis, and targeted treatment of silicosis. • Macrophage pyroptosis plays a critical role in silicosis progression and fibrosis. • NLRP3 inflammasome activation is central to macrophage pyroptosis in silicosis. • Dysbiosis of lung microbiota worsens silicosis by enhancing pyroptotic signaling. • Targeting pyroptosis-related pathways offers therapeutic potential for silicosis.