PMID- 28195158 OWN - NLM STAT- MEDLINE DCOM- 20181113 LR - 20190614 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 DP - 2017 Feb 14 TI - Infection-derived lipids elicit an immune deficiency circuit in arthropods. PG - 14401 LID - 10.1038/ncomms14401 [doi] LID - 14401 AB - 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. FAU - Shaw, Dana K AU - Shaw DK AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Wang, Xiaowei AU - Wang X AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Brown, Lindsey J AU - Brown LJ AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Chavez, Adela S Oliva AU - Chavez AS AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Reif, Kathryn E AU - Reif KE AD - Animal Disease Research Unit, United States Department of Agriculture, Agriculture Research Service, Pullman, Washington 99164, USA. FAU - Smith, Alexis A AU - Smith AA AD - Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA. FAU - Scott, Alison J AU - Scott AJ AD - Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA. FAU - McClure, Erin E AU - McClure EE AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Boradia, Vishant M AU - Boradia VM AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Hammond, Holly L AU - Hammond HL AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Sundberg, Eric J AU - Sundberg EJ AD - Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Snyder, Greg A AU - Snyder GA AD - Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. FAU - Liu, Lei AU - Liu L AD - Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA. FAU - DePonte, Kathleen AU - DePonte K AD - Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA. FAU - Villar, Margarita AU - Villar M AD - SaBio. Instituto de Investigacion en Recursos Cinegeticos IREC, CSIC-UCLM-JCCM, Ciudad Real 13005, Spain. FAU - Ueti, Massaro W AU - Ueti MW AD - Animal Disease Research Unit, United States Department of Agriculture, Agriculture Research Service, Pullman, Washington 99164, USA. FAU - de la Fuente, Jose AU - de la Fuente J AD - SaBio. Instituto de Investigacion en Recursos Cinegeticos IREC, CSIC-UCLM-JCCM, Ciudad Real 13005, Spain. AD - Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA. FAU - Ernst, Robert K AU - Ernst RK AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. AD - Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA. FAU - Pal, Utpal AU - Pal U AD - Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA. FAU - Fikrig, Erol AU - Fikrig E AUID- ORCID: 0000-0002-5884-6047 AD - Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA. AD - Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. FAU - Pedra, Joao H F AU - Pedra JH AD - Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. LA - eng GR - R01 AI093653/AI/NIAID NIH HHS/United States GR - R01 AI116523/AI/NIAID NIH HHS/United States GR - T32 AI007540/AI/NIAID NIH HHS/United States GR - T32 AI095190/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170214 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (Lipids) RN - 0 (Phosphatidylglycerols) RN - 0 (RNA, Small Interfering) RN - 0 (Recombinant Proteins) RN - 0 (Rel protein, Drosophila) RN - 0 (Transcription Factors) RN - 0 (X-Linked Inhibitor of Apoptosis Protein) RN - 0 (casp protein, Drosophila) RN - 0 (peptidoglycan recognition protein) RN - 81490-05-3 (1-palmitoyl-2-oleoylglycero-3-phosphoglycerol) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.3.2.23 (Uev1a protein, Drosophila) RN - EC 2.3.2.23 (ben protein, Drosophila) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - Immune Deficiency Disease SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - Anaplasma marginale/immunology/pathogenicity MH - Anaplasma phagocytophilum/immunology/pathogenicity MH - Animals MH - Arthropods/*immunology/metabolism MH - Borrelia burgdorferi/immunology/pathogenicity MH - Carrier Proteins MH - Disease Models, Animal MH - Drosophila Proteins/genetics/metabolism MH - Drosophila melanogaster/metabolism MH - Escherichia coli/genetics MH - Fas-Associated Death Domain Protein MH - Gene Silencing MH - HEK293 Cells MH - Humans MH - Immunologic Deficiency Syndromes/*immunology/*veterinary MH - Ixodes/*immunology/metabolism MH - Lipids/*adverse effects/*immunology MH - Lyme Disease/immunology MH - Phosphatidylglycerols/immunology MH - RNA, Small Interfering/metabolism MH - Recombinant Proteins MH - Signal Transduction MH - Transcription Factors/genetics/metabolism MH - Ubiquitin-Conjugating Enzymes/genetics/metabolism MH - Ubiquitin-Protein Ligases/metabolism MH - X-Linked Inhibitor of Apoptosis Protein/metabolism PMC - PMC5316886 COIS- The authors declare no competing financial interests. EDAT- 2017/02/15 06:00 MHDA- 2018/11/14 06:00 PMCR- 2017/02/14 CRDT- 2017/02/15 06:00 PHST- 2016/05/12 00:00 [received] PHST- 2016/12/22 00:00 [accepted] PHST- 2017/02/15 06:00 [entrez] PHST- 2017/02/15 06:00 [pubmed] PHST- 2018/11/14 06:00 [medline] PHST- 2017/02/14 00:00 [pmc-release] AID - ncomms14401 [pii] AID - 10.1038/ncomms14401 [doi] PST - epublish SO - Nat Commun. 2017 Feb 14;8:14401. doi: 10.1038/ncomms14401.