Challenge with Staphylococcus aureus induces a lipid response in newborn piglets

Abstract

Abstract The innate immune system provides the first line of defense against microbes. Epithelial cells recognize pathogen-associated molecular patterns and detection leads to induction of antimicrobial peptides, proinflammatory cytokines, and chemokines. Recent evidence suggests that antimicrobial lipids, including fatty acids and cholesteryl esters, are also important effectors in the innate mucosal defense of the airways. We have previously shown that cholesteryl linoleate and cholesteryl arachidonate are active against Pseudomonas aeruginosa and other bacteria, and that the expression of SOAT1, a key enzyme for cholesteryl ester biosynthesis, is increased in sinus mucosa of patients with chronic rhinosinusitis. The objective of this study was to further elucidate the regulation of antimicrobial lipid production by assessing the gene expression of enzymes involved in lipid biosynthesis in an in vivo pig infection model. Newborn pigs were challenged intratracheally with aerosolized heat-killed Staphylococcus aureus (n = 7) or saline (n = 5) and RNA was extracted from trachea tissues 4 h later. Gene expression of the enzymes SOAT1, FADS2, FASN and ACSL1 was statistically significantly increased (p < 0.05 in One-Way ANOVA) in infected animals. In a second experiment (n = 3 for each group), formalin fixed tissues were subjected to a lipid preservation protocol prior to processing for histology and staining with the lipophilic dye Oil Red O. We observed in the trachea of animals challenged with S. aureus an increased staining with Oil Red O consistent with increased lipid accumulation. These data provide evidence that infection leads to increased lipid biosynthesis further supporting the concept of lipid-mediated innate mucosal defense.