Dissecting the antimicrobial network orchestrated by the noncanonical IMD pathway in ticks

About This Grant

Abstract Arthropod-borne disease continues to be a significant source of morbidity and mortality worldwide. The ability of an arthropod to harbor and transmit pathogens is termed “vector competency”. Many factors influence vector competency, including how the arthropod immune system responds to the microbe. The intricacies of insect immunity have been well-studied owing to the model organism, Drosophila. In contrast, comparatively little is known about tick immunity, representing a fundamental knowledge gap in vector biology. Arthropod immune processes are now increasingly recognized as being divergent across species. We previously reported a noncanonical Immune Deficiency (IMD) signaling network in ticks that differs from what has been described in insects and restricts colonization and survival of the Lyme disease- causing spirochete Borrelia burgdorferi. The tick genome has orthologues to core signaling components of the IMD network, including the NF-κB-like transcription factor Relish, but lacks pathway-specific antimicrobial peptides (AMPs). How the tick IMD pathway exerts antimicrobial activity and what gene targets Relish transcriptionally upregulates remain unknown. To identify genes putatively regulated by Relish, we used a program that predicts transcriptional factor binding sites in arthropod genomes, ArthroQuest. We identified one putative Relish-regulated gene, tachylectin-5, with predicted antimicrobial and agglutinating functions. We found that Tachylectin-5 was also induced in tick cells infected with B. burgdorferi. Based on these findings, our central hypothesis is that Ixodes Relish upregulates the expression of Tachylectin- 5 and other antimicrobial effector molecules that restrict the Lyme disease spirochete B. burgdorferi. Aim 1 of this proposal will examine whether tachylectin-5 expression is driven by Relish. Aim 2 will investigate if B. burgdorferi is functionally restricted by Tachylectin-5. Aim 3 will seek to define the Relish-regulated transcriptional network in Ixodes ticks. The outcome of this proposal will provide insight into the molecular mechanisms that govern vector competence and immunity in ticks.