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

Xiaotian Tang,Yongguo Cao,Andaleeb Sajid,Jesse Hwang,Alejandro Marín-López,Utpal Pal,Courtney L Brown,Erol Fikrig,Sameet Mehta,Ming-Jie Wu,Hongwei Ma,Gunjan Arora,Sukanya Narasimhan,Yu-Min Chuang

doi:10.7554/elife.72568

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

Highlights

Adiponectin, adipocyte complement related protein of 30 kDa, plays important roles in the regulation of metabolism, insulin sensitivity, and inflammation across species (Kadowaki et al, 2006; Ouchi and Walsh, 2007; Yamauchi et al, 2002).Adiponectin mediates its actions mainly via binding adiponectin receptors with its globular C1q domain (Buechler et al, 2010; Yamauchi et al, 2002)
As tick metabolism changes during pathogen colonization, and adiponectinassociated pathways mediate diverse metabolic activities, we examined the I
As I. scapularis lack an obvious adiponectin homolog, we examined whether expression of ISARL could be stimulated in the feeding vector by allowing ticks to engorge on mice, including uninfected and B. burgdorferi-infected animals

Summary

Significance Statement

Adiponectin binds to adiponectin receptors and participates in glucose and lipid metabolism in mammals. We found that ticks have an adiponectin receptor-like protein but lack adiponectin. We demonstrated that the Lyme disease agent, Borrelia burgdorferi, takes advantage of the adiponectin receptor signaling pathway to establish infection in its arthropod vector, Ixodes scapularis. Our study sheds light on the understanding of Borrelia-tick interactions and provides insights into how a human infectious disease agent may evolve to manipulate host metabolism for its own benefits. Understanding this pathway may lead to new ways to interfere with the Borrelia life cycle, and this mechanism may be applicable to additional microbes that are transmitted by ticks, mosquitoes or other arthropods

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Ethics statement