Journal Article

Infection-derived lipids elicit an immune deficiency circuit in arthropods

Brown, Lindsey J., Smith, Alexis A., Snyder, Greg A., Fikrig, Erol, Villar, Margarita, Sundberg, Eric J., Wang, Xiaowei, Boradia, Vishant M., Reif, Kathryn E., Liu, Lei, de la Fuente, José, DePonte, Kathleen, Pedra, Joao H. F., Ueti, Massaro W., Shaw, Dana K., Chávez, Adela S. Oliva, Hammond, Holly L., Ernst, Robert K., Pal, Utpal, McClure, Erin E., Scott, Alison J.

2017

Overview

The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale . Cell signalling ensues in the absence of transmembrane peptidoglycan recognition proteins and the adaptor molecules Fas-associated protein with a death domain (FADD) and IMD. Conversely, biochemical interactions occur between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless. We propose the existence of two functionally distinct IMD networks, one in insects and another in ticks. The insect IMD signalling pathway detects invading pathogens. Here the authors show that ticks have an alternative IMD system that lacks peptidoglycan receptors, IMD and FADD, and is instead reliant on interaction of the E3 ligase XIAP with the E2 conjugating enzyme Bendless.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/89 / 13/95 / 631/250/255/1318 / 631/250/262/2106 / 631/601/1466 / 64 / 64/24 / 82/29 / 82/80 / 82/83 / 96/1 / Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - metabolism / Anaplasma marginale - immunology / Anaplasma marginale - pathogenicity / Anaplasma phagocytophilum - immunology / Anaplasma phagocytophilum - pathogenicity / Animals / Apoptosis / Arachnids / Arthropods / Arthropods - immunology / Arthropods - metabolism / Bacteria / Bacterial infections / Borrelia burgdorferi - immunology / Borrelia burgdorferi - pathogenicity / Carrier Proteins / Disease Models, Animal / Drosophila melanogaster - metabolism / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Enzymes / Escherichia coli - genetics / Fas-Associated Death Domain Protein / Gene Silencing / Genomes / Gram-negative bacteria / HEK293 Cells / Humanities and Social Sciences / Humans / Immunologic Deficiency Syndromes - immunology / Immunologic Deficiency Syndromes - veterinary / Immunology / Infections / Insects / Ixodes - immunology / Ixodes - metabolism / Kinases / Lipids / Lipids - adverse effects / Lipids - immunology / Lyme disease / Lyme Disease - immunology / multidisciplinary / Phosphatidylglycerols - immunology / Proteins / Recombinant Proteins / RNA, Small Interfering - metabolism / Science / Science (multidisciplinary) / Signal Transduction / Transcription Factors - genetics / Transcription Factors - metabolism / Tumor necrosis factor-TNF / Ubiquitin-Conjugating Enzymes - genetics / Ubiquitin-Conjugating Enzymes - metabolism / Ubiquitin-Protein Ligases - metabolism / Vector-borne diseases / Veterinary medicine / X-Linked Inhibitor of Apoptosis Protein - metabolism