O'Neal, Anya Josephine2023-02-142023-02-142022http://hdl.handle.net/10713/20357University of Maryland, Baltimore. Molecular Microbiology and Immunology. Ph.D. 2022.Innate immunity in metazoans relies on an arsenal of pattern recognition receptors. These molecules activate signaling pathways that direct antimicrobial defense. The arthropod immune system, which has been largely studied in the fruit fly Drosophila melanogaster, utilizes the immune deficiency (IMD) pathway to defend against Gram-negative bacteria. Recent studies using the blacklegged tick Ixodes scapularis determined that immune signaling in chelicerates is wired differently from dipteran insects. Notably, ticks and other chelicerates do not encode several components of the canonical IMD pathway, including classical receptors. Here, we report that the I. scapularis homolog of Croquemort (Crq), a CD36-like lipid scavenger receptor, initiates immune pathways against the Lyme disease spirochete Borrelia burgdorferi. Crq binds the lipid and IMD pathway agonist 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and exhibits plasma membrane localization. Nymphs silenced for crq display impaired fitness, an inability to reach full repletion, and delayed molting to adulthood due to deficient ecdysteroid synthesis. Importantly, Crq relays antimicrobial signals, regulates immune gene expression, and limits acquisition of B. burgdorferi through the IMD and jun N-terminal kinase (JNK) pathways. Collectively, our findings reveal an ancient antibacterial immune response in non-insect arthropods and establish a new scientific paradigm in tick-borne diseases.en-USLipidsImmunity, InnateTicksdissertation2023-02-10Pedra, Joao H. F.