Pathogen associated molecular pattern motifs from Gram-positive and Gram-negative bacteria induce different inflammatory mediator profiles in equine blood

Abstract

Although the incidence of Gram-positive infection in horses is increasing, little is known about differences in inflammatory response between Gram-positive and Gram-negative organisms in this species. Equine blood was stimulated with components of both Gram-negative and Gram-positive organisms: lipopolysaccharide (LPS); lipoteichoic acid (LTA); peptidoglycan (PG); with combinations of LPS, LTA and PG; and with phosphate buffered saline (control). LPS, LTA and PG stimulated tumor necrosis factor (TNF) and interleukin (IL)-6 production but only LTA and PG stimulated IL-1β production from whole blood. LPS was a more potent inducer of TNF than either LTA or PG and both LPS and LTA were more potent inducers of IL-6 than PG. Generally, combinations of pathogen associated molecular patterns (PAMPs) did not elicit greater inflammatory mediator responses when compared to LPS, LTA or PG alone, although there was some synergism between the effects of LPS and LTA. The repertoire of inflammatory mediators provoked by Gram-positive vs. Gram-negative motifs is thus distinctly different. As novel immunomodulatory therapies are developed for use in the horse, care should be exercised when applying treatments for endotoxemia to animals with Gram-positive infections given the different cytokine response profiles.