Cellular mechanisms underlying LPS-induced bactericidal activity in Dictyostelium discoideum (162.15)

Abstract

Cells of the innate immune system detect pathogen-associated molecular patterns (PAMPs) through highly conserved pattern-recognition machinery. The conservation of this machinery allows for its characterization in model organisms. The unique model organism Dictyostelium discoideum can exist as single-celled amoebae that phagocytize bacteria for nutritional uptake. However, it has not been determined if D. discoideum uses pattern-recognition machinery to detect PAMPs. Here we show that D. discoideum mounts a response against the bacterial cell wall PAMP, lipopolysaccharide (LPS). LPS treatment results in an increased clearance of phagoctyzed bacteria by D. discoideum. LPS-induced bactericidal activity appears to be dependent on MAPK and Tir domain-containing protein A (TirA)-mediated pathways. Recent results suggest that increased bactericidal activity upon treatment with LPS may involve the induction and maturation of autophagosomes. We show here, by following the delivery of the autophagosomal marker Atg8 to degradative compartments, that Staphylococcus aureus induces autophagosomal maturation in D. discoideum only upon addition of LPS. We are currently characterizing the signaling pathways underlying bacterial induction of autophagy in D. discoideum. Characterization of the cellular events induced upon microbial pattern recognition in D. discoideum should provide valuable insight into conversed cellular mechanisms underlying microbial detection and killing.