title: Infection-derived lipids elicit an immune deficiency circuit in arthropods.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Shaw
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Brown
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Adela S Oliva
authors.initials: AS
authors.lastname: Chávez
authors.affiliation: Animal Disease Research Unit, United States Department of Agriculture, Agriculture Research Service, Pullman, Washington 99164, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Reif
authors.affiliation: Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Smith
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Scott
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: McClure
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Vishant M
authors.initials: VM
authors.lastname: Boradia
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Holly L
authors.initials: HL
authors.lastname: Hammond
authors.affiliation: Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sundberg
authors.affiliation: Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Snyder
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: DePonte
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real 13005, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Villar
authors.affiliation: Animal Disease Research Unit, United States Department of Agriculture, Agriculture Research Service, Pullman, Washington 99164, USA.
authors.forename: Massaro W
authors.initials: MW
authors.lastname: Ueti
authors.affiliation: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real 13005, Spain.|Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
authors.forename: José
authors.initials: J
authors.lastname: de la Fuente
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.|Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.affiliation: Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
authors.forename: Erol
authors.identifier: 0000-0002-5884-6047
authors.initials: E
authors.lastname: Fikrig
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Joao H F
authors.initials: JH
authors.lastname: Pedra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D042322:Anaplasma marginale / Q000276:immunology / Q000472:pathogenicity; D041081:Anaplasma phagocytophilum / Q000276:immunology / Q000472:pathogenicity; D000818:Animals; D001181:Arthropods / Q000276:immunology* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000276:immunology / Q000472:pathogenicity; D002352:Carrier Proteins; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D053200:Fas-Associated Death Domain Protein; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000662:veterinary*; D018884:Ixodes / Q000276:immunology* / Q000378:metabolism; D008055:Lipids / Q000009:adverse effects* / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology; D010715:Phosphatidylglycerols / Q000276:immunology; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D053200:Fas-Associated Death Domain Protein; D008055:Lipids; D010715:Phosphatidylglycerols; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C101626:Rel protein, Drosophila; D014157:Transcription Factors; D051636:X-Linked Inhibitor of Apoptosis Protein; C515596:casp protein, Drosophila; C118897:peptidoglycan recognition protein; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D044763:Ubiquitin-Conjugating Enzymes; C583339:Uev1a protein, Drosophila; C471544:ben protein, Drosophila; D044767:Ubiquitin-Protein Ligases