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Title: Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods

Author
item SHAW, DANA - University Of Maryland
item BROWN, LINDSEY - University Of Maryland
item Reif, Kathryn
item SMITH, ALEXIS - University Of Maryland
item SCOTT, ALISON - University Of Maryland
item MCCLURE, ERIN - University Of Maryland
item SUNDBERG, ERIC - University Of Maryland
item SNYDER, GREG - University Of Maryland
item Ueti, Massaro
item PEDRA, JOAO - University Of Maryland

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/29/2016
Publication Date: 2/14/2017
Citation: Shaw, D.K., Brown, L.J., Reif, K.E., Smith, A.A., Scott, A., McClure, E., Sundberg, E., Snyder, G., Ueti, M.W., Pedra, J.H. 2017. Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods. Nature Communications. doi:10.1038/ncomms14401.

Interpretive Summary: The insect Immune Deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties elicit the IMD signaling cascade remains unknown. We disclose though lipidomics analysis and functional assays that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol and 1-palmitoyl-2-oleoyl diacylglycerol stimulate the IMD pathway and protects against bacterial infection in ticks of veterinary and public health relevance. Understanding this IMD pathway is important to develop strategies to prevent pathogens to be transmit by arthropod vector. In this study, we propose the existence of functionally distinct IMD networks: one termed classical and occurring in insects, and another displayed in ticks.

Technical Abstract: The insect Immune Deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties elicit the IMD signaling cascade remains unknown. Here, we disclose though lipidomics analysis and functional assays that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway and protects against bacterial infection in ticks of veterinary and public health relevance. Notably, the Ixodes scapularis IMD signaling cascade is activated upon colonization by the Lyme disease agent Borrelia burgdorferi and the rickettsial pathogen Anaplasma phagocytophilum. This molecular circuitry ensued independently of the protein FADD and the adaptor molecule IMD and occurred through the interaction between the E3 ubiquitin ligase XIAP and the E2 conjugating enzyme Bendless. Altogether, we propose the existence of functionally distinct IMD networks: one termed classical and occurring in insects, and another displayed in ticks.