Association of TLR4 polymorphism with cytokine expression level and pulmonary lesion score in pigs

Abstract

The toll-like receptor 4 (TLR4), recognizing lipopolysaccharide of gram-negative bacteria, plays an essential role in immune responses. Variation in TLR4 alters host immune responses to pathogen and is associated with resistance/susceptibility to infectious diseases, as suggested by studies in humans and agricultural species, including cattle and chicken. In this study, we analyzed association of single nucleotide polymorphisms (SNPs) of TLR4 with cytokine expression level and pulmonary lesion score in swine. The SNP c.611 T>A showed significant association with the transcription levels of IFNG, TNFA, and IL-6 (P < 0.05); the SNP c.962 G>A showed significant association with the transcription of IFNG, IL-2, and IL-4 (P < 0.05); the SNP c.1,027 C>A showed significant association with the transcription of IFNG and IL-6 (P < 0.05); the haplotypes showed significant association with the transcription of IFNG, IL-2, IL-4, IL-6, and TNFA (P < 0.05). Both SNPs c.611 T>A and c.962 G>A showed significant association with pulmonary lesion scores (P < 0.01); and the combination genotypes of 3 polymorphic sites were also significantly associated with pulmonary lesion scores (P < 0.01). The observed relationship between TLR4 polymorphism and the transcription levels of cytokines indicate that these SNPs are related to the modulation of the cytokine mediated immune response.