The Lyme disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector.

Abstract

Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that <i>Ixodes scapularis</i> ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin, suggesting activation by alternative pathways. <i>ISARL</i> expression is significantly upregulated in the tick gut after <i>Borrelia burgdorferi</i> infection, suggesting that ISARL signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of <i>ISARL</i> significantly reduced the <i>B. burgdorferi</i> burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with <i>B. burgdorferi</i> survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and <i>B. burgdorferi</i> facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete.