Epigenetic Regulation of Tick Biology and Vectorial Capacity.

Ticks exist across diverse environments and transmit numerous pathogens. Due to their long and unique life cycles, these arthropods likely evolved robust epigenetic mechanisms that provide sustainable responses and buffers against extreme environmental conditions. Herein, we highlight how the study of the epigenetic basis of tick biology and vectorial capacity will enrich our knowledge of tick-borne infections.

Environmental and ecological factors affecting tick infestation in wild birds of the Americas.

The Americas hold the greatest bird diversity worldwide. Likewise, ectoparasite diversity is remarkable, including ticks of the Argasidae and Ixodidae families - commonly associated with birds. Considering that ticks have potential health implications for humans, animals, and ecosystems, we conducted a systematic review to evaluate the effects of bioclimatic, geographic variables, and bird species richness on tick infestation on wild birds across the Americas. We identified 72 articles that met our inclusion criteria and provided data on tick prevalence in wild birds. Using Generalized Additive Models, we assessed the effect of environmental factors, such as habitat type, climatic conditions, bird species richness, and geographic location, on tick infestation. Our findings show that most bird infestation case studies involved immature ticks, such as larvae or nymphs, while adult ticks represented only 13% of case studies. We found birds infested by ticks of the genera Amblyomma (68%), Ixodes (22%), Haemaphysalis (5%), Dermacentor (1%), and Rhipicephalus (0.8%) in twelve countries across the Americas. Our findings revealed that temperature variation and bird species richness were negatively associated with tick infestation, which also varied with geographic location, increasing in mid-latitudes but declining in extreme latitudes. Our results highlight the importance of understanding how environmental and bird community factors influence tick infestation in wild birds across the Americas and the dynamics of tick-borne diseases and their impact on biodiversity.

Risk factors contributing to tick-acaricide control failure in communal areas of the Oliver Tambo district eastern cape province, South Africa.

Application of chemical acaricides in the control of ticks has led to the problem of tick-acaricide control failure. To obtain an understanding of the possible risk factors involved in this tick-acaricide control failure, this study investigated tick control practices on communal farms in the north-eastern part of the Eastern Cape Province (ECP) of South Africa. A semi-structured questionnaire designed to document specific farm attributes and acaricide usage practices was administered at 94 communal farms from the Oliver Tambo District municipality of the ECP. Data collected indicated that the main acaricide chemicals used at plunge dips of inland and coastal areas were synthetic pyrethroid formulations. Most (75%) farmers claimed not to have noticed a significant reduction in numbers of actively feeding and growing ticks on cattle after several acaricide treatments. Based on the farmers' perceptions, leading factors that could have led to tick-acaricide control failure included: weak strength of the dip solution (76%); poor structural state of dip tanks (42%); and irregular tick control (21%). The rearing of crossbreeds of local and exotic cattle breeds, perceived weak strength of the dip solution and high frequency of acaricide treatment, were statistically associated with proportions of farms reporting tick-acaricide control failure. Furthermore, approximately 50% of farms reported at least four tick control malpractices, which could have resulted in the emergence and spread of tick-acaricide control failure. Other sub-optimal tick control practices encountered included incorrect acaricide rotation, and failure to treat all cattle in a herd. This data will inform and guide the development of management strategies for tick-acaricide control failure and resistance in communal farming areas.

The tick and I: Parasite-host interactions between ticks and humans.

Ticks, particularly hard ticks (Ixodidae), which are among the most important vectors of dangerous infectious agents, feed on their hosts for extended periods of time. With this lifestyle, numerous adaptations have evolved in ticks and their hosts, the pharmacological importance of which is increasingly being recognized. Many bioactive substances in tick saliva are being considered as the basis of new drugs. For example, components of tick cement can be developed into tissue adhesives or wound closures. Analgesic and antipruritic salivary components inhibit histamine or bradykinin, while other tick-derived molecules bind opioid or cannabinoid receptors. Tick saliva inhibits the extrinsic, intrinsic, or common pathway of blood coagulation with implications for the treatment of thromboembolic diseases. It contains vasodilating substances and affects wound healing. The broad spectrum of immunomodulatory and immunosuppressive effects of tick saliva, such as inhibition of chemokines or cellular immune responses, allows development of drugs against inflammation in autoimmune diseases and/or infections. Finally, modern vaccines against ticks can curb the spread of serious infections. The medical importance of the complex tick-host interactions is increasingly being recognized and translated into first clinical applications. Using selected examples, an overview of the mutual adaptations of ticks and hosts is given here, focusing on their significance to medical advance.

Acquired tick resistance: The trail is hot.

Acquired tick resistance is a phenomenon wherein the host elicits an immune response against tick salivary components upon repeated tick infestations. The immune responses, potentially directed against critical salivary components, thwart tick feeding, and the animal becomes resistant to subsequent tick infestations. The development of tick resistance is frequently observed when ticks feed on non-natural hosts, but not on natural hosts. The molecular mechanisms that lead to the development of tick resistance are not fully understood, and both host and tick factors are invoked in this phenomenon. Advances in molecular tools to address the host and the tick are beginning to reveal new insights into this phenomenon and to uncover a deeper understanding of the fundamental biology of tick-host interactions. This review will focus on the expanding understanding of acquired tick resistance and highlight the impact of this understanding on anti-tick vaccine development efforts.

Tick salivary gland transcriptomics and proteomics.

'Omics' technologies have facilitated the identification of hundreds to thousands of tick molecules that mediate tick feeding and play a role in the transmission of tick-borne diseases. Deep sequencing methodologies have played a key role in this knowledge accumulation, profoundly facilitating the study of the biology of disease vectors lacking reference genomes. For example, the nucleotide sequences of the entire set of tick salivary effectors, the so-called tick 'sialome', now contain at least one order of magnitude more transcript sequences compared to similar projects based on Sanger sequencing. Tick feeding is a complex and dynamic process, and while the dynamic 'sialome' is thought to mediate tick feeding success, exactly how transcriptome dynamics relate to tick-host-pathogen interactions is still largely unknown. The identification and, importantly, the functional analysis of the tick 'sialome' is expected to shed light on this 'black box'. This information will be crucial for developing strategies to block pathogen transmission, not only for anti-tick vaccine development but also the discovery and development of new, pharmacologically active compounds for human diseases.

Recent advances in understanding tick and rickettsiae interactions.

Ticks are haematophagous arthropods with unique molecular mechanisms for digesting host blood meal while acting as vectors for various pathogens of public health significance. The tick's pharmacologically active saliva plays a fundamental role in modulating the host's immune system for several days to weeks, depending on the tick species. The vector tick has also developed sophisticated molecular mechanisms to serve as a competent vector for pathogens, including the spotted fever group (SFG) rickettsiae. Evidence is still inadequate concerning tick-rickettsiae-host interactions and saliva-assisted transmission of the pathogen to the mammalian host. Rickettsia parkeri, of the SFG rickettsia, can cause a milder version of Rocky Mountain spotted fever known as American Boutonneuse fever. The Gulf Coast tick (Amblyomma maculatum) often transmits this pathogenic rickettsia in the USA. This review discusses the knowledge gap concerning tick-rickettsiae-host interactions by highlighting the SFG rickettsia and the Am maculatum model system. Filling this knowledge gap will provide a better understanding of the tick-rickettsiae-host interactions in disease causation, which will be crucial for developing effective methods for preventing tick-borne diseases.

Tick-virus interactions: Current understanding and future perspectives.

Ticks are the primary vector of arboviruses in temperate climates worldwide. They are both the vector of these pathogens to humans and an integral component of the viral sylvatic cycle. Understanding the tick-pathogen interaction provides information about the natural maintenance of these pathogens and informs the development of countermeasures against human infection. In this review, we discuss currently available information on tick-viral interactions within the broader scope of general tick immunology. While the tick immune response to several pathogens has been studied extensively, minimal work centres on responses to viral infection. This is largely due to the high pathogenicity of tick-borne viruses; this necessitates high-containment laboratories or low-pathogenicity substitute viruses. This has biased most research towards tick-borne flaviviruses. More work is required to fully understand the role of tick-virus interaction in sylvatic cycling and transmission of diverse tick-borne viruses.

Ticks (Acari: Ixodoidea) associated with mammals in Colombia: a historical review, molecular species confirmation, and establishment of new relationships.

Ticks are considered the second most important vectors of pathogens worldwide, after mosquitoes. This study provides a systematic review of vector-host relationships between ticks and mammals (domestic and wild) and consolidates information from studies conducted in Colombia between 1911 and 2020. Using the PRISMA method, 71 scientific articles containing records for 51 tick species (Argasidae and Ixodidae) associated with mammals are reported. The existing information on tick-mammal associations in Colombia is scarce, fragmented, or very old. Moreover, 213 specimens were assessed based on morphological and molecular analyses, which allowed confirming eight tick species associated with mammals: Amblyomma calcaratum, Amblyomma dissimile, Amblyomma mixtum, Amblyomma nodosum, Amblyomma ovale, Amblyomma varium, Ixodes luciae, and Ixodes tropicalis. Several tick species are molecularly confirmed for Colombia and nine new relationships between ticks and mammals are reported. This research compiles and confirms important records of tick-mammal associations in Colombia.

Parasites of wombats (family Vombatidae), with a focus on ticks and tick-borne pathogens.

Ticks (Arachnida: Acari) are vectors for pathogens and the biggest threat to animal health. Many Australian ticks are associated with pathogens that impact humans, domestic animals and livestock. However, little is known about the presence or impact of tick-borne pathogens in native Australian wildlife. Wombats are particularly susceptible to the effects of the ectoparasite Sarcoptes scabiei which causes sarcoptic mange, the reason for which is unknown. Factors such as other ectoparasites and their associated pathogens may play a role. A critical understanding of the species of ectoparasites that parasitise wombats and their pathogens, and particularly ticks, is therefore warranted. This review describes the ectoparasites of wombats, pathogens known to be associated with those ectoparasites, and related literature gaps. Pathogens have been isolated in most tick species that typically feed on wombats; however, there are minimal molecular studies to determine the presence of pathogens in any other wombat ectoparasites. The development of next-generation sequencing (NGS) technologies allows us to explore entire microbial communities in ectoparasite samples, allowing fast and accurate identification of potential pathogens in many samples at once. These new techniques have highlighted the diversity and uniqueness of native ticks and their microbiomes, including pathogens of potential medical and veterinary importance. An increased understanding of all ectoparasites that parasitise wombats, and their associated pathogens, requires further investigation.

Ticks and tick-borne pathogens infecting livestock and dogs in Tchicala-Tcholoanga, Huambo Province, Angola.

The diversity of ticks and tick-borne pathogens (TBPs) infesting domestic animals in Tchicala-Tcholoanga, Angola, in 2016 was investigated. Seventeen tick species were recorded, Amblyomma pomposum being the most abundant on cattle (40%), goats (38%) and sheep (35%); Rhipicephalus turanicus was the most abundant on dogs (46%). This study presents new records of Haemaphysalis paraleachi, R. compositus, R. kochi and R. sulcatus in Angola, the first georeferenced population of Ha. leachi in southern Africa and the second record of R. microplus in Angola. Using the reverse line blot (RLB) hybridisation assay, fifteen TBP species were detected in blood samples from cattle (n = 88), goats (n = 82), sheep (n = 85) and dogs (n = 85). F The most frequently detected species were Theileria velifera in cattle (78%), Theileria ovis in sheep (80%) and Babesia vogeli in dogs (35%). Species-specific quantitative PCR assays detected Babesia bigemina in 43% (35/80) of blood samples of cattle, while E. ruminantium was detected in 4% (3/70) of blood samples and in 7% of A. pomposum ticks. Anaplasma platys was detected from cattle (18%) and sheep (6%) during RLB analysis. These findings constitute pioneering research in Angola.

Hepatozoon canis in hunting dogs from Southern Italy: distribution and risk factors.

Hepatozoon canis is a hemoprotozoan organism that infects domestic and wild carnivores throughout much of Europe. The parasite is mainly transmitted through the ingestion of infected ticks containing mature oocysts. The aims of the present survey were to determine the prevalence of H. canis in hunting dogs living in Southern Italy and to assess potential infection risk factors. DNA extracted from whole blood samples, collected from 1433 apparently healthy dogs living in the Napoli, Avellino, and Salerno provinces of Campania region (Southern Italy), was tested by a quantitative real-time polymerase chain reaction (qPCR) assay to amplify H. canis. Furthermore, the investigated dog population was also screened by qPCR for the presence of Ehrlichia canis, a major tick-borne pathogen in Southern Italy, in order to assess possible co-infections. Two hundred dogs were H. canis PCR-positive, resulting in an overall prevalence of 14.0% (CI 12.2-15.9). Breed category (P < 0.0001), hair coat length (P = 0.015), and province of residence (P < 0.0001) represented significant risk factors for H. canis infection. The presence of H. canis DNA was also significantly associated with E. canis PCR positivity (P < 0.0001). Hunting dogs in Campania region (Southern Italy) are frequently exposed to H. canis, and the infection is potentially associated with close contact with wildlife. Further studies are needed to assess the pathogenic potential of H. canis, as well as the epidemiological relationships between hunting dogs and wild animal populations sharing the same habitats in Southern Italy.

Identification of tick-borne pathogens in ticks collected from wild animals in Turkey.

Many enzootic life cycles involving wild animals and non-nidicolous ixodids are still unknown. Therefore, the aim of this study was to report the identified tick species collected from seven different animal species (red deer, brown bear, gray wolf, Eurasian lynx, red fox, European hare, and Mediterranean spur-thighed tortoise) living in the wild in Turkey and to investigate the presence of a wide range of tick-borne microorganisms in the tick samples obtained from these animals. The collected ticks (n = 98) were identified as Dermacentor reticulatus, Haemaphysalis parva, Hyalomma aegyptium, Hyalomma excavatum, Hyalomma marginatum, Ixodes ricinus, and Rhipicephalus turanicus. All engorged ticks collected from the wild animals and unfed larvae (n = 30) obtained from a single Rh. turanicus female were also analyzed individually for tick-borne bacterial and protozoan agents via PCR-sequencing. The molecular analyses revealed the presence of Babesia sp. tavsan2, Theileria capreoli, four Hepatozoon spp. (Hep. ursi, Hep. canis, Hep. felis, and Hepatozoon sp.), Hemolivia mauritanica, and three SFG rickettsiae (Candidatus Rickettsia barbariae, Ca. R. goldwasserii, and Rickettsia hoogstraalii) in the collected ticks. This represents the first report of Th. capreoli, Hep. ursi, and Ca. R. barbariae in ticks from Turkey. The evolutionary relationships of microbes in the different host and tick species are also discussed. Multiple novel tick-host associations in the tick life cycle were also revealed.

Immunological Responses to the Relapsing Fever Spirochete Borrelia turicatae in Infected Rhesus Macaques: Implications for Pathogenesis and Diagnosis.

The global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with Borrelia turicatae (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate that B. turicatae elicits from peripheral blood cells key inflammatory response mediators (interleukin-1ß and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.

Ticks (Acari: Ixodida) on birds (Aves) migrating through the Polish Baltic coast.

Seasonal bird (Aves) migration between breeding and wintering areas, often located on different continents, can facilitate the spreading of tick species (Acari: Ixodida) and of tick-borne pathogens. The aim of the study was to analyse the occurrence of ticks dispersed by birds migrating along the Polish Baltic coast during spring and autumn migration. Field research was conducted at the bird ringing station in Wicie, located on the middle of the Polish Baltic coast, in 2011 and 2012 during spring and autumn migration. A total of 2657 birds from 45 species was examined. The most common species inspected were European robin (Erithacus rubecula) (63.3%), song thrush (Turdus philomelos) (5.13%), and goldcrest (Regulus regulus) (4.5%). Overall, 3129 ticks belonging to six species were collected: Ixodes ricinus (1650 larvae, 1390 nymphs and 1 male), Ixodes frontalis (20 larvae, 20 nymphs), Ixodes arboricola (35 larvae), Dermacentor reticulatus (1 larva), and Haemaphysalis punctata (1 nymph). Ten larvae and one nymph could only be identified to the genus level Ixodes. Ticks were located on various parts of the head: on the corner of the beak (75.0%), near the eyes (14.6%), on the chin (4.4%), near the ears (4.4%), on the neck (1.1%), and in the beak (0.5%). The overall tick prevalence was 40.5%. The highest prevalence was for bird species feeding on the ground, covering a medium distance to wintering grounds and migrating at night. Statistically significant differences between the number of ticks and the sex of the host species were detected in blackbirds: males carried more parasites than females, both, during spring and autumn migration. The fact that I. ricinus and other ticks parasitize birds migrating through Poland extends the possibility of the spread of tick-borne diseases.

Borrelia burgdorferi SpoVG DNA- and RNA-Binding Protein Modulates the Physiology of the Lyme Disease Spirochete.

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations.IMPORTANCEB. burgdorferi persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that B. burgdorferi controls production of SpoVG and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression of spoVG exerts effects on bacterial replication and other aspects of the spirochete's physiology.

Tick-borne diseases and autoimmunity: A comprehensive review.

Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.

Peptidase inhibitors in tick physiology.

Peptidase inhibitors regulate a wide range of physiological processes involved in the interaction between hematophagous parasites and their hosts, including tissue remodeling, the immune response and blood coagulation. In tick physiology, peptidase inhibitors have a crucial role in adaptation to improve parasitism mechanisms, facilitating blood feeding by interfering with defense-related host peptidases. Recently, a larger number of studies on this topic led to the description of several new tick inhibitors displaying interesting novel features, for example a role in pathogen transmission to the host. A comprehensive review discussing these emerging concepts can therefore shed light on peptidase inhibitor functions, their relevance to tick physiology and their potential applications. Here, we summarize and examine the general characteristics, functional diversity and action of tick peptidase inhibitors with known physiological roles in the tick-host-pathogen interaction.

The multiple roles of peroxiredoxins in tick blood feeding.

Hydrogen peroxide (H2O2) and hydroxyl radicals (HO·) are generated through partial reduction of oxygen. The HO· are the most reactive and have a shorter half-life than H2O2, they are produced from comparatively stable H2O2 through Fenton reaction. Although controlling HO· is important and biologically advantageous for organisms, it may be difficult. Ticks are obligate hematophagous arthropods that need blood feeding for development. Ticks feed on vertebrate blood containing high levels of iron. Ticks also concentrate iron-containing host blood, leading to high levels of iron in ticks. Host-derived iron may react with oxygen in the tick body, resulting in high concentrations of H2O2. On the other hand, ticks have antioxidant enzymes, such as peroxiredoxins (Prxs), to scavenge H2O2. Gene silencing of Prxs in ticks affects their blood feeding, oviposition, and H2O2 concentration. Therefore, Prxs could play important roles in ticks' blood feeding and oviposition through the regulation of the H2O2 concentration. This review discusses the current knowledge of Prxs in hard ticks. Tick Prxs are also multifunctional molecules related to antioxidants and immunity like other organisms. In addition, tick Prxs play a role in regulating the host immune response for ticks' survival in the host body. Tick Prx also can induce Th2 immune response in the host. Thus, this review would contribute to the further understanding of the tick's antioxidant responses during blood feeding and the search for a candidate target for tick control.