The role of autophagy in tick-endosymbiont interactions: insights from Ixodes scapularis and Rickettsia buchneri

ABSTRACT Approximately 80 identified tick species are recognized as vectors and impact global public health by transmitting a wide range of pathogens; however, little is known about the interactions of ticks with the microbiome that they harbor, let alone their bacterial symbionts. In this study, we used the black-legged tick, Ixodes scapularis Say (Acari: Ixodidae), a vector of seven human pathogens in the United States, and utilized Rickettsia buchneri sensu stricto ISO7T (Rickettsiales: Rickettsiaceae), a spotted fever group (SFG) rickettsia that is an endosymbiont of I. scapularis, to investigate the role of autophagy in symbiont and tick interactions. We found that the expression profile of most autophagy family member proteins (ATGs) is down-regulated after R. buchneri infection in tick cell cultures. The autophagic process was observed by assessment of autophagosome formation and maturation in vitro (tick cell culture) and in vivo (tick ovary) in the presence of R. buchneri, whereas apoptosis was not induced. We further showed that R. buchneri infection triggered the accumulation of plasma membranes within cells. Suppressing autophagy via Atg8 siRNA interference inhibited intracellular rickettsial replication. This research indicates that autophagy regulation is important for the maintenance of R. buchneri in its I. scapularis tick host and provides more clues to solve the tick-symbiont interaction puzzle. IMPORTANCE Ticks are second only to mosquitoes in their importance as vectors of disease agents; however, tick-borne diseases (TBDs) account for the majority of all vector-borne disease cases in the United States (approximately 76.5%), according to Centers for Disease Control and Prevention reports. Newly discovered tick species and their associated disease-causing pathogens, and anthropogenic and demographic factors also contribute to the emergence and re-emergence of TBDs. Thus, incorporating different tick control approaches based on a thorough knowledge of tick biology has great potential to prevent and eliminate TBDs in the future. Here we demonstrate that replication of a transovarially transmitted rickettsial endosymbiont depends on the tick’s autophagy machinery but not on apoptosis. Our findings improve our understanding of the role of symbionts in tick biology and the potential to discover tick control approaches to prevent or manage TBDs. Ticks are second only to mosquitoes in their importance as vectors of disease agents; however, tick-borne diseases (TBDs) account for the majority of all vector-borne disease cases in the United States (approximately 76.5%), according to Centers for Disease Control and Prevention reports. Newly discovered tick species and their associated disease-causing pathogens, and anthropogenic and demographic factors also contribute to the emergence and re-emergence of TBDs. Thus, incorporating different tick control approaches based on a thorough knowledge of tick biology has great potential to prevent and eliminate TBDs in the future. Here we demonstrate that replication of a transovarially transmitted rickettsial endosymbiont depends on the tick’s autophagy machinery but not on apoptosis. Our findings improve our understanding of the role of symbionts in tick biology and the potential to discover tick control approaches to prevent or manage TBDs.