Croquemort elicits activation of the immune deficiency pathway in ticks

• Type of Material: Article
• Authors: Anya J. O'Neal, University of Maryland, Baltimore; Nisha Singh, University of Maryland, Baltimore; Agustin Rolandelli, University of Maryland, Baltimore; Hanna J. Laukaitis, University of Maryland, Baltimore; Xiaowei Wang, University of Maryland, Baltimore; Dana K. Shaw, University of Maryland, Baltimore; Brianna D. Young, University of Maryland, Baltimore; Sukanya Narasimhan, Yale University; Shraboni Dutta, University of Maryland, College Park; Greg A. Snyder, University of Maryland, Baltimore; Sourabh Samaddar, University of Maryland, Baltimore; Liron Marnin, University of Maryland, Baltimore; L. rainer Butler, University of Maryland, Baltimore; m. tays Mendes, University of Maryland, Baltimore; Francy E. Cabrera Paz, University of Maryland, Baltimore; Luisa M. Valencia, University of Maryland, Baltimore; Eric John Sundberg, Emory University; Erol Fikrig, Yale University; Utpal Pal, University of Maryland, College Park; David J. Weber, University of Maryland, Baltimore; Joao H.F. Pedra, University of Maryland, Baltimore
• Language: English
• Date: 2023-05-08
• Publisher: PNAS
• Publication Version: Final Published Version
• Copyright Statement: © 2023 the Author(s).
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1073/pnas.2208673120
• Title of Journal or Parent Work: Immunology and Inflammation
• Volume: 120
• Issue: 20
• Start Page: e2208673120
• Grant/Funding Information: This work was supported by grants from the NIH to A.J.O. (F31AI152215), L.R.B. (F31AI167471), J.H.F.P. (R01AI134696, R01AI116523, R01AI049424), J.H.F.P., E.F., and U.P. (P01AI138949), U.P. (R01AI080615, R01AI116620), D.J.W. (R01GM129327, R56AI52397), and D.K.S. (R21AI139772, R21AI148578) and the National Institute of Standards and Technology (NIST) to D.J.W. (70NANB18H252). J.H.F.P. was also supported in-kind by the Fairbairn Family Lyme Research Initiative.
• Keywords: arthropod immunology; ticks; entomology
• Research Categories: Biology, Entomology; Health Sciences, Immunology; Biology, Molecular

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.