Skin Colonization with S. aureus Can Lead to Increased NLRP1 Inflammasome Activation in Patients with Atopic Dermatitis

The role of NLRP1 inflammasome activation and subsequent production of IL-1 family cytokines in the development of atopic dermatitis (AD) is not clearly understood. Staphylococcus aureus is known to be associated with increased mRNA levels of IL1 family cytokines in the skin and more severe AD. In this study, the altered expression of IL-1 family cytokines and inflammasome-related genes was confirmed, and a positive relationship between mRNA levels of inflammasome sensor NLRP1 and IL1B or IL18 was determined. Enhanced expression of the NLRP1 and PYCARD proteins and increased caspase-1 activity were detected in the skin of patients with AD. The genetic association of IL18R1 and IL18RAP with AD was confirmed, and the involvement of various immune cell types was predicted using published GWAS and expression quantitative trait loci datasets. In keratinocytes, the inoculation with S. aureus led to the increased secretion of IL-1b and IL-18, whereas small interfering RNA silencing of NLRP1 inhibited the production of these cytokines. Our results suggest that skin colonization with S. aureus may cause the activation of the NLRP1 inflammasome in keratinocytes, which leads to the secretion of IL-1b and IL-18 and thereby may contribute to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.

Automated summary

The study confirms the alteration in expression of IL-1 family cytokines and inflammasome-related genes in the development of atopic dermatitis (AD), and a positive relationship between NLRP1 and IL1B or IL18 mRNA levels. It also demonstrates increased expression of NLRP1 and PYCARD proteins, and increased caspase-1 activity in the skin of AD patients. Additionally, genetic associations with AD and the involvement of various immune cell types are predicted. In keratinocytes, colonization with Staphylococcus aureus results in increased secretion of IL-1b and IL-18, which is inhibited by siRNA silencing of NLRP1. These findings suggest that S. aureus colonization may activate the NLRP1 inflammasome in keratinocytes, leading to the secretion of IL-1b and IL-18, and contributing to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.