Toll-Like Receptor Characterization Correlates with Asthma and Is Predictive of Diagnosis

Abstract

Toll-like receptors (TLRs) play crucial roles in the recognition of invading pathogens and the immune system. However, the effect of TLRs in asthma is still not fully known. This study was performed to better understand the role of TLR signatures in asthma. Blood samples from case-control studies (study 1: 348 asthmas and 39 normal controls and validation study 2: 411 asthmas and 87 normal controls) were enrolled. The single-sample gene set enrichment analysis method was performed to quantify the abundance of 21 TLR signatures. Gene ontology analysis and pathway function analysis were conducted for functional analysis, and a protein-protein interaction network was constructed. The area under the curve (AUC) value was used to assess the diagnostic capacity. In this study, TLR2/TLR3/TLR4 pathway, MyD88-dependent/independent TLR pathway, positive regulation of TLR4 pathway, and TLR binding signatures were significantly higher in asthma. Functional analysis showed that biological processes and pathways were still involved in TLR cascades and TLR signaling pathway. Eleven hub TLR-related genes were identified, and further validation demonstrated that the combination of TLR-related genes was a good diagnostic biomarker for asthma (AUC = 0.8). Our study provided more insight into the underlying immune mechanism of how TLR signatures affected asthma. The use of the easy-to-apply TLR-related genes might represent a promising blood-based biomarker for early detection of asthma.