Peromyscus leucopus,Mus musculus, and humans have distinct transcriptomic responses to larvalIxodes scapularisbites

Abstract

AbstractIxodes scapularisticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirocheteBorrelia burgdorferi. The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without excessive activation of the proinflammatory branch of the vertebrate immune system. While the ability for nymphal ticks to feed on a variety of hosts has been well-documented, the host-parasite interactions between larvalI. scapularisand different vertebrate hosts is relatively unexplored. Here we report on the changes in the vertebrate transcriptome present at the larval tick bite site using the naturalI. scapularishostPeromyscus leucopusdeermouse, a non-natural rodent hostMus musculus(BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways inP. leucopuscompared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite site. We also note that bite sites on BALB/c mice and humans, but not deermice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larvalI. scapularisandP. leucopusas well as expand our overall understanding ofI. scapularisfeeding.SignificanceIxodes scapularistick bites expose humans to numerous diseases in North America. While larval tick feeding enables pathogens to enter the tick population and eventually spread to humans, how larval ticks interact with mammals has been understudied compared to other tick stages. Here we examined the transcriptomic response of a naturalI. scapularisrodent host (Peromyscus leucopus), a non-nativeI. scapularisrodent host (Mus musculus), and an incidental host (humans). We find that there are differences in how all three species respond to larvalI. scapularis, with the natural host producing the smallest transcriptomic signature of a canonical proinflammatory immune response and the incidental human host producing the most robust signature of inflammation in response to the larval tick. These data expand our understanding of the pressures on ticks in the wild and inform our ability to model these interactions in laboratory settings.