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Nat Commun. 2017 Feb 14;8:14401. doi: 10.1038/ncomms14401.

Infection-derived lipids elicit an immune deficiency circuit in arthropods.

Author information

1
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
2
Animal Disease Research Unit, United States Department of Agriculture, Agriculture Research Service, Pullman, Washington 99164, USA.
3
Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA.
4
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland 21201, USA.
5
Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
6
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
7
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real 13005, Spain.
8
Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
9
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

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.

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