Stimulating innate immunity in feedlot cattle: strategies to induce tracheal antimicrobial peptide gene expression

Abstract

Bovine respiratory disease (BRD) is an economically devastating complex of bacterial and viral infections that greatly affects the feedlot industry across North America. Studies have shown that viral infections such as BVDV and glucocorticoid production in stressed calves may inhibit the induction of tracheal antimicrobial peptide (TAP), a cationic β‐defensin that has direct microbicidal effects on invading microbes in the respiratory tract. Certain surface receptors of the innate immune system called the Toll‐Like‐Receptors (TLRs) recognize pathogen associated molecular patterns (PAMPs) to initiate intracellular signal transduction pathways that potentially induce TAP gene expression. PCR analyses of unstimulated tracheal epithelial cells show mRNA expression for TLRs 1,2,3,4, and 6. Therefore, stimulation of tracheal epithelial cells with agonists for these TLRs may induce TAP expression. Previous studies have shown that a TLR 4 agonist called Lipopolysaccharide (LPS) significantly induces TAP expression in epithelial cells after 16 hours of stimulation. This suggests that LPS induces TAP expression via the TLR 4 pathway. The present study examines TLR 2 agonists to determine their effect on TAP induction. Quantitative Real‐Time PCR analysis of epithelial cells stimulated by the TLR 2 agonist Lipoteichoic Acid has shown significant induction of TAP. However, the amount of induction is much less than LPS and occurs after the same amount of stimulation time. Future experiments will determine if other TLR 2 agonists can induce gene expression of TAP in a robust and rapid manner so that TAP production can be increased to ultimately reduce the incidence of BRD in feedlot calves.