NLRP3 inflammasome is attenuated in patients with Mycobacterium avium complex lung disease and correlated with decreased interleukin-1β response and host susceptibility
Journal
Scientific Reports
Journal Volume
9
Journal Issue
1
Date Issued
2019
Author(s)
Wu M.-F.
Wu L.S.-H.
Abstract
The incidence of nontuberculous mycobacteria lung disease (NTM-LD) is increasing in patients without human immunodeficiency virus. Mycobacterium avium complex (MAC) is one of the most common pathogenic species. The presence of MAC has a clinical relevance of around 35~42%, indicating the possibility of host susceptibility. Previous studies have shown that interleukin (IL)-1β and IL-1-receptor knock-out mice are susceptible to mycobacterial infections; however, the role of inflammasome-driven interleukin (IL)-1β has not been studied in MAC-LD. We enrolled patients with MAC-LD and healthy controls. Peripheral blood mononuclear cells (PBMCs), monocytes, and monocyte-derived macrophages were stimulated by MAC bacilli. The responses of interleukin(IL)-1β and the expression of inflammasome and toll-like receptors (TLRs) were measured. Single nucleotide polymorphisms (SNPs) were also examined for NLRP3 and TLR2 genes. In the patients with MAC-LD, the IL-1β responses decreased in PBMCs, monocytes, and macrophages assayed by MAC bacilli in comparison to the healthy controls. In addition, the level of caspase-1 after stimulation was lower in the MAC-LD group, although the mRNA level of IL-1β was not significantly lower. In surveying the activation of IL-1β, the MAC-LD group had an attenuated mRNA level of NLRP3 but similar levels of AIM2 and ASC compared with the controls. The SNPs rs3806268 and rs34298354 in NLRP3 for females and rs3804100 in TLR2 for males were associated with MAC-LD. In conclusion, our patients with MAC-LD had attenuated IL-1β production, which may have been due to lower activation of the NLRP3-caspase-1 axis. Two SNPs of NLRP3 and one of TLR2 were correlated with MAC-LD, possibly indicating host susceptibility. ? 2019, The Author(s).
SDGs
Other Subjects
cryopyrin; IL1B protein, human; inflammasome; interleukin 1beta; NLRP3 protein, human; TLR2 protein, human; toll like receptor 2; adult; atypical mycobacteriosis; female; genetic predisposition; genetics; human; immunology; male; microbiology; middle aged; mononuclear cell; Mycobacterium avium complex; physiology; prospective study; single nucleotide polymorphism; young adult; Adult; Female; Genetic Predisposition to Disease; Humans; Inflammasomes; Interleukin-1beta; Leukocytes, Mononuclear; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; NLR Family, Pyrin Domain-Containing 3 Protein; Polymorphism, Single Nucleotide; Prospective Studies; Toll-Like Receptor 2; Young Adult
Publisher
Nature Publishing Group
Type
journal article