MRNA vaccination induces tick resistance and prevents transmission of the Lyme Disease agent
Ontology highlight
ABSTRACT:
ORGANISM(S): Cavia porcellus
PROVIDER: GSE184063 | GEO | 2021/09/13
REPOSITORIES: GEO
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Project description:Ixodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment. Four milimeter ear biopsies from BALB/cJ mice infested with Ixodes scapularis nymphs were assayed using Affymetrix genechip 430A 2.0 arrays at 1, 3, 6, and 12 hours after infestation during a primary exposure. 3 mice were measured at each time point. Controls were 3 similarly housed but tick-free mice.
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Project description:Borrelia burgdorferi, the etiological agent of Lyme disease, persists in nature through an enzootic cycle consisting of a vertebrate host and an Ixodes tick vector. The sequence motifs modified by two well-characterized restriction/modification loci of B. burgdorferi type strain B31 were recently described, but the methylation profiles of other Lyme disease Borrelia have not been characterized. Herein, the methylomes of B. burgdorferi type strain B31 and 7 clonal derivatives, along with B. burgdorferi N40, B. burgdorferi 297, B. burgdorferi CA-11, B. afzelii PKo, B. afzelii BO23, and B. garinii PBr, were defined through PacBio SMRT sequencing. This analysis revealed 9 novel sequence motifs methylated by the plasmid-encoded restriction/modification enzymes of these Borrelia strains. Furthermore, while a previous analysis of B. burgdorferi B31 revealed an epigenetic impact of methylation on the global transcriptome, the current data contradict those findings; our analyses of wild-type B. burgdorferi B31 revealed no consistent differences in gene expression among isogenic derivatives lacking one or more restriction/modification enzyme(s).
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Project description:Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to vertebrate hosts by Ixodes ticks. As it moves from tick to host, B. burgdorferi must adapt to survive in a vastly different environment. During the tick bloodmeal, which lasts several days, B. burgdorferi is primed for mammalian infection, growing increasingly virulent as it senses cues from its surroundings in the tick. This conditioning is dependent on key transcriptional regulators; however, the downstream transcriptional changes occurring inside of the tick that promote B. burgdorferi transmission and infection are poorly understood due to technical difficulties in sequencing the B. burgdorferi transcriptome from inside of ticks. We developed a protocol to enrich and sequence B. burgdorferi from inside the tick, and we measured global transcriptional changes occurring in feeding ticks. We identified 192 genes that change expression twofold over the course of the tick bloodmeal, which were predominantly located on the plasmids of the genome. The majority of the upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 upregulated genes encoding outer surface lipoproteins. These genes that increase during feeding are candidates for future functional studies, which can help identify new targets for methods that aim to control the spread of Lyme disease.
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Project description:To understand the immunomodulation roles of Ixodes scapularis protein disulfide isomerase A6 (IsPDIA6), we utilized RNA sequencing (RNA-seq) to investigate the effect of IsPDIA6 on the murine transcriptome.
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Project description:To compare the transcriptional profiles of Borrelia burgdorferi (Bb) during acquisition (fed larvae), transmission (fed nymphs) and in a mammalian host-like environment (dialysis membrane chambers [DMC]).RNA was isolated from an infected tick (Ixodus scapularis) samples, DMC and in vitro cultures. Array hybridization was performed with 7 RNA samples (from 5 biological replicates) obtained from fed nymphs and 10 RNA samples (from 6 biological replicates) obtained from fed larvae. Mammalian host-adapted spirochetes were generated by growth in DMCs. 4 arrays (2 biological replicates) were performed with DMC samples and in vitro-cultivated (temperature-shifted) samples.RNA was labeled with Cy3and as an internal standard for array hybridization, B. burgdorferi genomic DNA was labeled with Cy5 hybridized to Bb 70-mer slide arrays.Signal was acquired on a GenePix scanner. Background subtracted intensities obtained for each gene were normalized to one reference array using Microsoft Excel. Normalized data sets were further refined using GeneSpring software. A gene was scored as expressed if pixel intensity was >75 and was detected in a majority of arrays for given condition. Differentially expressed genes were identified as those with a fold change >2 at P<0.02 through gene-by-gene comparison of normalized expression data sets using an unpaired t-test within GeneSpring GX12.5.
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Project description:Ixodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
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Project description:Ticks are blood feeding arthropod ectoparasites that transmit pathogens, which cause diseases in humans and animals worldwide. In the past ten decades, the continuous human exploitation of environmental resources and the increase in human outdoor activities has promoted contact with arthropod vectors normally present in the wild, resulting in increased transmission of vector-borne pathogens. In addition, vector populations are expanding in response to climate change and human interventions that impact reservoir host movement and human exposure to infected vectors. Among these emerging vector-borne pathogens, Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) has become an important tick-borne pathogen in the United States, Europe and Asia, with increasing numbers of infected people and animals every year. Diseases caused by A. phagocytophilum include human granulocytic anaplasmosis (HGA), equine and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. The natural infection cycle of A. phagocytophilum is dependent upon the presence of infected vertebrate reservoir hosts and Ixodid tick vectors. In the United States and Europe the main vector species are Ixodes scapularis, Ixodes pacificus, and Ixodes ricinus, while a wide range of mammals, lizards, and birds serve as reservoir hosts for various A. phagocytophilum genotypes. A. phagocytophilum initially infects tick midgut cells and then subsequently develops in salivary glands for transmission to susceptible hosts during tick feeding where the pathogen infects granulocytic cells, primarily neutrophils. Anaplasma phagocytophilum develops within membrane-bound inclusions in the host cell cytoplasm. This pathogen has evolved with its tick and vertebrate hosts through dynamic processes involving genetic traits of the pathogen and hosts that collectively mediate pathogen infection, development, persistence, and survival. However, the mechanisms used by A. phagocytophilum for molecular mechanisms involved in tick-pathogen interactions have not been fully characterized. The objective of this study is to characterize the dynamics of the microRNA response in the tick vector Ixodes scapularis in response to A. phagocytophilum infection. To address this objective, the composition of tick microRNAs was characterize using RNA sequencing in I. scapularis tick cells in response to A. phagocytophilum infection. The discovery of these mechanisms provides evidence that a control strategy could be developed targeted at both vertebrate and tick hosts for more complete control of A. phagocytophilum and its associated diseases.
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