Low‐Molecular Weight Branched Polyethylenimine Reduces Cytokine Secretion from Human Immune System Monocytes Stimulated with Bacterial and Fungal PAMPs

Abstract

Adaptive immunity recruits T‐cells and specific antibodies against antigens, innate immune cells express pathogen recognition receptors (PRRs) that can detect various pathogen‐associated molecular patterns (PAMPs) released by invading pathogens. Microbial molecular patterns, such as lipopolysaccharide (LPS) from Gram‐negative bacteria, trigger signaling cascades in the host that result in the production of pro‐inflammatory cytokines. LPS stimulation produces a strong immune response and excessive LPS signaling leads to dysregulation of the immune response. However, dysregulated inflammatory response during wound healing often results in chronic non‐healing wounds that are difficult to control. In this work, we present data demonstrating partial neutralization of anionic LPS molecules using cationic branched polyethylenimine (BPEI). The anionic sites on the LPS molecules from Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the lipid A moiety and BPEI binding create steric factors that hinder the binding of PRR signaling co‐factors. This reduces the production of pro‐inflammatory TNF‐α cytokines. However, the anionic sites of Pseudomonas aeruginosa (P. aeruginosa) LPS are in the O‐antigen region and subsequent BPEI binding slightly reduces TNF‐α cytokine production. Fortunately, BPEI can reduce TNF‐α cytokine expression in response to stimulation by intact P. aeruginosa bacterial cells and fungal zymosan PAMPs.