Croquemort elicits activation of the immune deficiency pathway in ticks

Author:

O’Neal Anya J.1,Singh Nisha1,Rolandelli Agustin1ORCID,Laukaitis Hanna J.1ORCID,Wang Xiaowei1,Shaw Dana K.12ORCID,Young Brianna D.3ORCID,Narasimhan Sukanya4,Dutta Shraboni5ORCID,Snyder Greg A.6,Samaddar Sourabh1ORCID,Marnin Liron1,Butler L. Rainer1,Mendes M. Tays1ORCID,Cabrera Paz Francy E.1,Valencia Luisa M.1,Sundberg Eric J.167ORCID,Fikrig Erol4ORCID,Pal Utpal5ORCID,Weber David J.3ORCID,Pedra Joao H. F.1ORCID

Affiliation:

1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201

2. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164

3. Department of Biochemistry and Molecular Biology, Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201

4. Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510

5. Department of Veterinary Medicine, University of Maryland, College Park, MD 20742

6. Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201

7. Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

Abstract

The immune deficiency (IMD) pathway directs host defense in arthropods upon bacterial infection. In Pancrustacea, peptidoglycan recognition proteins sense microbial moieties and initiate nuclear factor-κB-driven immune responses. Proteins that elicit the IMD pathway in non-insect arthropods remain elusive. Here, we show that an Ixodes scapularis homolog of croquemort (Crq), a CD36-like protein, promotes activation of the tick IMD pathway. Crq exhibits plasma membrane localization and binds the lipid agonist 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoglycerol. Crq regulates the IMD and jun N-terminal kinase signaling cascades and limits the acquisition of the Lyme disease spirochete B. burgdorferi . Additionally, nymphs silenced for crq display impaired feeding and delayed molting to adulthood due to a deficiency in ecdysteroid synthesis. Collectively, we establish a distinct mechanism for arthropod immunity outside of insects and crustaceans.

Funder

HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

DOC | National Institute of Standards and Technology

Fairbairn Family Lyme Disease Research Initiative

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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