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Impaired interferon-γ signaling promotes the development of silicosis

Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine worker...

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Detalles Bibliográficos
Autores principales: Peng, Zhouyangfan, Duan, Mingwu, Tang, Yiting, Wu, Jianfeng, Zhao, Kai, Zhong, Yanjun, He, Zhihui, Meng, Jie, Chen, Fangping, Xiao, Xianzhong, Wang, Haichao, Billiar, Timothy R., Lu, Ben, Liang, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254453/
https://www.ncbi.nlm.nih.gov/pubmed/35800765
http://dx.doi.org/10.1016/j.isci.2022.104647
Descripción
Sumario:Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine workers with silicosis and their co-workers who did not develop silicosis revealed that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. Global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the crystalline silica-induced pulmonary injury in wild-type but not in NLRP3 deficient mice. In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas volumes to resistant crystalline silica-induced lysosomal membrane damage. Thus, these findings provide molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants.