Project description:Alpha-gal syndrome (AGS) is a delayed allergic response to red meat caused by the production of alpha-gal-specific IgE following certain tick bites. We designed this study to characterize the underlying immune response to tick bites associated with AGS. Our results suggest that Amblyomma americanum bites direct mouse immunity toward Th2 following the initial burst of proinflammatory response and facilitate host sensitization to the α-gal antigen.
Project description:Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms asso-ciated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events, and that the time course of these signals may align with local pathophysiology. As a first step to-wards testing this hypothesis, we contrasted molecular signatures in skin biopsies taken from the tick-bite location of human participants along with peripheral blood signatures obtained at the same time. This approach captures differentially expressed molecules across multiple omics da-tasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our data re-vealed that extracellular matrix organisation and platelet degranulation pathways were upregu-lated in skin within 72 hours of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the poten-tial value of blood samples, akin to liquid biopsy, to capture biomarkers reflecting local tissue processes.
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.
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.
Project description:In this study, we immunized guinea pigs with mRNA of Salp14 C terminus and lipid nanoparticles (LNP), the animals produced high titers of IgG, and developed moderate erythema during tick challenge, the transcriptomes of skin at tick bite sites enriched multiple immune response pathways, which might be involved in erythema development.
Project description:Ticks are widely distributed ectoparasitic arthropods that suck blood from the body surface of livestock, wild animals, and humans. Ticks not only transmit a variety of pathogens but also cause various degrees of damage to their hosts' skin during blood feeding. To explore the molecular regulatory mechanism employed by the host skin to withstand tick bites, larval, nymphal, and adult Haemaphysalis longicornis, which is distributed in East Asia, were used to bite the skin tissues of healthy rabbits in the present study. The quantitative proteomic technology data-independent acquisition was then employed to investigate in depth the changes in protein expression and phosphorylation in rabbit skin after tick bite. The results showed that among the 4034 proteins and 1795 phosphorylated proteins identified, a total of 202 proteins and 435 phosphorylation sites were changed at all time points after H. longicornis bite. Regulated host proteins such as coronin, mannose receptor C-type 1, dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), ezrin, and integrin play important roles in immune defence against tick bite. Fibrinogen, fibronectin, integrin-linked kinase (ILK), and tenascin C jointly regulate the coagulation and wound healing processes in the host. Trichohyalin and peptidyl arginine deiminase 3 were downregulated to induce hair loss in the host. In addition, the changes in the phosphorylation of interleukin-4 receptor, microtubule-actin crosslinking factor 1, and Nck adaptor protein 1 would play important roles in host immunity and vascular repair.
Project description:Powassan virus (POWV), a vector-borne pathogen transmitted by Ixodes ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick-feeding and salivary factors modulate the host's immunological responses, facilitating blood feeding and pathogen transmission. However, the mechanisms of immunomodulation during POWV transmission remain inadequately understood. In this study, we investigated the global cutaneous transcriptomic changes associated with tick bites during POWV transmission. We collected skin biopsies from the tick attachment sites at 1-, 3-, and 6-hours post-feeding by POWV-infected and uninfected ticks, followed by RNA sequencing of these samples. Differentially expressed genes were analyzed for pathway enrichment using gene ontology and pathway enrichment analyses. Our findings reveal that tick feeding alone significantly impacts the skin transcriptome within the first 1 to 3 hours of tick attachment. Although early POWV transmission induces minimal changes in the local environment, a pronounced shift toward a proinflammatory state is observed 6 hours post tick attachment, characterized by neutrophil recruitment and interleukin signaling. These transcriptomic data elucidate the dynamic changes at the tick bite site, transitioning from changes that assist blood meal acquisition to a proinflammatory phase that may facilitate viral dissemination.
Project description:This experiment was undertaken to document changes in gene expression in the skin of tick-resistant Brahman (Bos indicus) and tick-susceptible Holstein-Friesian (Bos taurus) cattle prior to, and following, infestation with the cattle tick Rhipicephalus (Boophilus) microplus Keywords: Disease state analysis