Cellular mechanisms linking pattern recognition and autophagy in Dictyostelieum discoideum (169.19)

Abstract

Pattern recognition machinery is used by cells of the innate immune system to detect conserved patterns on invading pathogens. Dictyostelieum discoideum is a model organism that phagocytizes bacteria for nutritional purposes, and we have shown recently that D. discoideum may use conserved pattern recognition machinery to detect and respond to their bacterial prey, since D. discoideum cells stimulated with the microbial pattern lipopolysaccharide (LPS) more efficiently clear phagocytized bacteria. Here we extend these findings, showing that LPS stimulates maturation of autophagosomes and transport of autophagosomal contents to lysosomes in D. discoideum cells exposed to Staphylococcus aureus. Induction of autophagy appears sufficient for increased bacterial killing in D. discoideum cells, as D. discoideum clears bacteria at in increased rate when cells are treated with the autophagy-inducing drug, rapamycin. Finally, we illustrate that LPS-enhanced transport of phagocytized S. aureus to the degradative lysosomes is significantly reduced in D. discoideum cells lacking the autophagy-related protein Atg1 or the toll/interleukin-1 receptor domain-containing protein TirA. Thus, for the first time, we link microbial pattern recognition and autophagy in this model organism, providing greater understanding of the highly conserved mechanisms underlying pathogen detection.