Biology subjects

Telford, S. R.

Publications and source records attributed to Telford, S. R..

3 recordsLinked to original sources

bioRxiv2024

Peromyscus leucopus, Mus musculus, and humans have distinct transcriptomic responses to larval Ixodes scapularis bites

Ixodes scapularis ticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirochete Borrelia 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 larval I. scapularis and 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 natural I. scapularis host Peromyscus leucopus deermouse, a non-natural rodent host Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared 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 larval I. scapularis and P. leucopus as well as expand our overall understanding of I. scapularis feeding. SignificanceIxodes scapularis tick 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 natural I. scapularis rodent host (Peromyscus leucopus), a non-native I. scapularis rodent host (Mus musculus), and an incidental host (humans). We find that there are differences in how all three species respond to larval I. 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.

immunology↗

bioRxiv2023

Low-cost camera-based estrous tracking enables transgenesis in Peromyscus leucopus, the primary reservoir for Lyme disease

CRISPR/Cas9 technology has revolutionized the production of animal models by reducing experimental timelines, slashing costs and streamlining gene editing, leading to a rapid expansion in the number of unique models for the study of human disease and gene function. However, most non-model animals, many of which are important in cancer and aging research, remain recalcitrant to genome engineering due to our limited understanding of their reproductive biology. Many wild rodents that transmit human diseases remain particularly challenging to engineer due to low pregnancy rates, the lack of external copulatory plugs, and susceptibility to premature termination of pregnancy. Here, we present low-cost activity-based estrous tracking for the efficient generation of timed pregnant and pseudopregnant white-footed mice and extend this tracking method to both lab mice and hamsters. Leveraging this technology, we demonstrate the generation of engineered Peromyscus leucopus, the primary reservoir for Lyme disease-causing bacteria and a putative model organism for studies of aging. These tools have broad implications for biomedical research and ecological engineering. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/563285v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@19a3fb2org.highwire.dtl.DTLVardef@1cbce4corg.highwire.dtl.DTLVardef@1551e0corg.highwire.dtl.DTLVardef@127c028_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Strain-dependent assessment of Powassan virus transmission to deer ticks.

1.Powassan virus (POWV) is an emergent tick-borne encephalitis virus of Lyme disease endemic sites in North America. Due to range expansion and local intensification of deer tick vector (Ixodes scapularis) populations in the northeastern and upper midwestern U.S., encephalitis cases are increasingly being reported. A better understanding of the transmission cycle of POWV may allow for predicting the eventual public health burden. Recent phylogeographic analyses of POWV have identified geographical structuring, with well-defined northeastern and midwestern clades of the deer tick virus subtype (lineage II); sublineages exist within each clade. It may be that the local sublineages differ in their capacity to be transmitted by the deer tick vector. Accordingly, we determined whether there are strain-dependent differences in transmission. Five recent, low passage POWV isolates were used to measure aspects of vector competence, using viremic and artificial infection methods. Infection rates in experimental ticks remained consistent between all five isolates tested, resulting in 12-20% infection rate and no clear differences in viral load. We conclude that there is a genotype independent ability of POWV to infect deer ticks, and that differences in transmission efficiency are not likely to serve as the basis for regional differences in apparent public health burden.

microbiology↗