Upregulation of Genes for Innate Immune Signaling and Apoptosis after Surgery for Chronic Rhinosinusitis: Evidence of a Mucosal Immune Dysfunction in CRS?

Abstract

Objective: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis is a frequently performed surgical procedure. However, the mechanism by which it improves disease is unknown. We wished to determine patterns of changes in gene expression associated with resolution of disease following ESS in order to identify mechanisms implicated in resolution of disease. Method: Twelve patients undergoing ESS for CRS were recruited. An epithelial sample from the frontal sinus was collected using a cytology brush at time of surgery and repeated 3 months after surgery. Microarray analysis of gene expression was performed using the Illumina Human HT-12 Beachip v3. Results: Both single gene expression analysis (using Limma package from Bioconductor software.) and gene set analysis (using Ingenuity Pathway Analysis software) were used to identify implicated genes and pathways (or networks), respectively. All patients resolved CRS with surgery. A total of 4707 genes or transcripts showed significant differential expression changes (pFDR). Healing was associated with increased expression of cytokines and transcription factors in the IL1B signaling pathway (IL8 (FC: 8.56; P = .00027) IL1B (FC: 4.21; P = .0008) NFkBIZ (FC: 2.27; P = .0008), innate immune signaling (IRAKs-1, -2, and -3, CD14, MD2, MyD88), and apoptosis (CASP3, BAK, BID). Conclusion: Resolution of CRS after ESS is characterized by marked upregulation of the IL-1B and innate immune signaling pathways and increased expression of pro-apoptosis genes. This supports the concept that microbial detection and clearance are impaired in CRS, and that strategies increasing immune activation may represent novel therapeutic opportunities.