Gene expression analysis in human polymorphonuclear leukocytes stimulated by LPSs from nosocomial opportunistic pathogens

Abstract

Innate immunity coordinates LPS detection via TLR4 on polymorphonuclear leukocytes (PMNs) to elicit responses to many Gram-negative bacteria. In this study, we describe the effects of five subtypes of LPS [isolated from Escherichia coli B4, Pseudomonas aeruginosa PAO1, multidrug-resistant P. aeruginosa (MDRP), Acinetobacter baumannii and multidrug-resistant A. baumannii (MDRA)] on gene expression in PMNs. LPS isolated from B4, PAO1, and A. baumannii did not significantly alter TLR2 expression. However, LPS from MDRP and MDRA caused a 0.6-fold decrease and 2.7-fold increase, respectively, in TLR2 expression. Similarly, TLR4 expression was not significantly altered by LPS isolated from B4, PAO1 and A. baumannii but was down-regulated by LPS isolated from MDRP and MDRA by 0.1- and 0.6-fold, respectively. All LPS subtypes, excluding PAO1, down-regulated CD14 expression in PMNs. However, all five LPS subtypes up-regulated TNFA, IL1B, IL6, IL10 and TREM1 expression in a concentration-dependent manner, with the most substantial responses observed following exposure to LPS from MDRP and MDRA. These different effects on the gene expression in PMNs may depend on variation in LPS structural modifications related to acquired drug resistance, such as acylation and/or glycosylation.