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Veterinary Sciences
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Comparative Studies in Tick-Borne Diseases in Animals and Humans
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Comparative Studies in Tick-Borne Diseases in Animals and Humans

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: closed (31 August 2016) | Viewed by 95198

Special Issue Editor

Prof. Dr. Ulrike Munderloh

E-Mail Website
Guest Editor
Department of Entomology, University of Minnesota, 1980 Folwell Avenue, St. Paul, MN 55108, USA
Interests: anaplasma; ehrlichia; rickettsia; genomics; mutagenesis; functional genomics; gene expression in ticks and mammals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tick-borne zoonotic disease agents have been causing a steady rise in illnesses in humans and domestic animals during the past 50 years or so, with a noticeable uptick in the rate of increase at the turn of the millennium. Although tick-borne diseases occur world-wide, the majority of human cases are reported in the temperate zones, whereas livestock-specific tick-borne pathogens, such as the bovine anaplasmosis, babesiosis, and heartwater agents, are found wherever there are cattle and competent vector ticks parasitizing them. Besides an increase in human and animals’ diseases due to pathogens transmitted by ticks, there has been an expansion in the range of several tick species, facilitated by movement of infested wild or domestic animals, and changes in habitat. Taken together, these events have altered the dynamics of tick ecology, with consequences that have enhanced exposure of humans and domestic animals, especially companion animals, to ticks and therefore tick-borne disease risk. The threat of zoonotic tick-borne pathogens that is shared between humans and animals highlights the need to strengthen the One Health approach to effectively tackle the challenges presented, especially since all tick-borne pathogens have animal reservoirs. It has long been understood that a focus on human disease alone cannot unveil all of the intricacies of tick borne zoonoses. This issue on "Comparative Studies in Tick-Borne Diseases in Animals and Humans" addresses this need to strengthen the flow and exchange of information between veterinary and medical sciences through publication of a selection of research articles from leading laboratories in this field. It is hoped that this issue will further stimulate collaboration between scientists engaged in all aspects of tick-borne disease research.

Prof. Dr. Ulrike Munderloh
Guest Editor

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Keywords

  • ticks
  • tick-borne pathogens
  • tick-borne zoonotic agents
  • Anaplasma
  • Ehrlichia
  • Rickettsia
  • Borrelia
  • Babesia
  • anaplasmosis
  • ehrlichiosis
  • rickettsioses
  • spotted fever
  • tick typhus
  • borreliosis
  • Lyme disease
  • relapsing fever
  • babesiosis
  • encephalitis
  • tick-borne encephalitis
  • Powassan virus
  • hemorrhagic fever
  • tick bite fever
  • lamb pyemia
  • sheep
  • goat
  • cattle
  • dog
  • horse
  • deer
  • human
  • wild rodents

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Published Papers (13 papers)

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Editorial

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137 KiB  
Editorial
Comparative Studies in Tick-Borne Diseases in Animals and Humans
by Ulrike Munderloh
Vet. Sci. 2017, 4(2), 32; https://doi.org/10.3390/vetsci4020032 - 20 Jun 2017
Cited by 4 | Viewed by 4137
Abstract
In temperate zones of the earth, ticks are the most important arthropod vectors of zoonotic pathogens affecting humans and domestic animals.[...] Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)

Research

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18304 KiB  
Article
Fluorescent Protein Expressing Rickettsia buchneri and Rickettsia peacockii for Tracking Symbiont-Tick Cell Interactions
by Timothy J. Kurtti, Nicole Y. Burkhardt, Chan C. Heu and Ulrike G. Munderloh
Vet. Sci. 2016, 3(4), 34; https://doi.org/10.3390/vetsci3040034 - 17 Nov 2016
Cited by 20 | Viewed by 6661
Abstract
Rickettsiae of indeterminate pathogenicity are widely associated with ticks. The presence of these endosymbionts can confound a One Health approach to combatting tick-borne diseases. Genomic analyses of symbiotic rickettsiae have revealed that they harbor mutations in gene coding for proteins involved in rickettsial [...] Read more.
Rickettsiae of indeterminate pathogenicity are widely associated with ticks. The presence of these endosymbionts can confound a One Health approach to combatting tick-borne diseases. Genomic analyses of symbiotic rickettsiae have revealed that they harbor mutations in gene coding for proteins involved in rickettsial pathogenicity and motility. We have isolated and characterized two rickettsial symbionts—Rickettsia peacockii and R. buchneri—both from ticks using tick cell cultures. To better track these enigmatic rickettsiae in ticks and at the tick-mammal interface we transformed the rickettsiae to express fluorescent proteins using shuttle vectors based on rickettsial plasmids or a transposition system driving insertional mutagenesis. Fluorescent protein expressing R. buchneri and R. peacockii will enable us to elucidate their interactions with tick and mammalian cells, and track their location and movement within individual cells, vector ticks, and host animals. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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7739 KiB  
Article
Microscopic Visualisation of Zoonotic Arbovirus Replication in Tick Cell and Organ Cultures Using Semliki Forest Virus Reporter Systems
by Lesley Bell-Sakyi, Sabine Weisheit, Claudia Rückert, Gerald Barry, John Fazakerley and Rennos Fragkoudis
Vet. Sci. 2016, 3(4), 28; https://doi.org/10.3390/vetsci3040028 - 29 Sep 2016
Cited by 6 | Viewed by 5803
Abstract
Ticks are vectors and reservoirs of many arboviruses pathogenic for humans or domestic animals; in addition, during bloodfeeding they can acquire and harbour pathogenic arboviruses normally transmitted by other arthropods such as mosquitoes. Tick cell and organ cultures provide convenient tools for propagation [...] Read more.
Ticks are vectors and reservoirs of many arboviruses pathogenic for humans or domestic animals; in addition, during bloodfeeding they can acquire and harbour pathogenic arboviruses normally transmitted by other arthropods such as mosquitoes. Tick cell and organ cultures provide convenient tools for propagation and study of arboviruses, both tick-borne and insect-borne, enabling elucidation of virus-tick cell interaction and yielding insight into the mechanisms behind vector competence and reservoir potential for different arbovirus species. The mosquito-borne zoonotic alphavirus Semliki Forest virus (SFV), which replicates well in tick cells, has been isolated from Rhipicephalus, Hyalomma, and Amblyomma spp. ticks removed from mammalian hosts in East Africa; however nothing is known about any possible role of ticks in SFV epidemiology. Here we present a light and electron microscopic study of SFV infecting cell lines and organ cultures derived from African Rhipicephalus spp. ticks. As well as demonstrating the applicability of these culture systems for studying virus-vector interactions, we provide preliminary evidence to support the hypothesis that SFV is not normally transmitted by ticks because the virus does not infect midgut cells. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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7830 KiB  
Article
Anaplasma phagocytophilum-Occupied Vacuole Interactions with the Host Cell Cytoskeleton
by Hilary K. Truchan, Chelsea L. Cockburn, Levi J. May, Lauren VieBrock and Jason A. Carlyon
Vet. Sci. 2016, 3(3), 25; https://doi.org/10.3390/vetsci3030025 - 21 Sep 2016
Cited by 13 | Viewed by 6031
Abstract
Anaplasma phagocytophilum is an obligate intracellular bacterial pathogen of humans and animals. The A. phagocytophium-occupied vacuole (ApV) is a critical host-pathogen interface. Here, we report that the intermediate filaments, keratin and vimentin, assemble on the ApV early and remain associated with the [...] Read more.
Anaplasma phagocytophilum is an obligate intracellular bacterial pathogen of humans and animals. The A. phagocytophium-occupied vacuole (ApV) is a critical host-pathogen interface. Here, we report that the intermediate filaments, keratin and vimentin, assemble on the ApV early and remain associated with the ApV throughout infection. Microtubules localize to the ApV to a lesser extent. Vimentin, keratin-8, and keratin-18 but not tubulin expression is upregulated in A. phagocytophilum infected cells. SUMO-2/3 but not SUMO-1 colocalizes with vimentin filaments that surround ApVs. PolySUMOylation of vimentin by SUMO-2/3 but not SUMO-1 decreases vimentin solubility. Consistent with this, more vimentin exists in an insoluble state in A. phagocytophilum infected cells than in uninfected cells. Knocking down the SUMO-conjugating enzyme, Ubc9, abrogates vimentin assembly at the ApV but has no effect on the bacterial load. Bacterial protein synthesis is dispensable for maintaining vimentin and SUMO-2/3 at the ApV. Withaferin A, which inhibits soluble vimentin, reduces vimentin recruitment to the ApV, optimal ApV formation, and the bacterial load when administered prior to infection but is ineffective once vimentin has assembled on the ApV. Thus, A. phagocytophilum modulates cytoskeletal component expression and co-opts polySUMOylated vimentin to aid construction of its vacuolar niche and promote optimal survival. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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1413 KiB  
Article
An Evaluation of Quantitative PCR Assays (TaqMan® and SYBR Green) for the Detection of Babesia bigemina and Babesia bovis, and a Novel Fluorescent-ITS1-PCR Capillary Electrophoresis Method for Genotyping B. bovis Isolates
by Bing Zhang, Jacqueline L. Sambono, Jess A. T. Morgan, Bronwyn Venus, Peter Rolls and Ala E. Lew-Tabor
Vet. Sci. 2016, 3(3), 23; https://doi.org/10.3390/vetsci3030023 - 13 Sep 2016
Cited by 10 | Viewed by 6669
Abstract
Babesia spp. are tick-transmitted haemoparasites causing tick fever in cattle. In Australia, economic losses to the cattle industry from tick fever are estimated at AUD$26 Million per annum. If animals recover from these infections, they become immune carriers. Here we describe a novel [...] Read more.
Babesia spp. are tick-transmitted haemoparasites causing tick fever in cattle. In Australia, economic losses to the cattle industry from tick fever are estimated at AUD$26 Million per annum. If animals recover from these infections, they become immune carriers. Here we describe a novel multiplex TaqMan qPCR targeting cytochrome b genes for the identification of Babesia spp. The assay shows high sensitivity, specificity and reproducibility, and allows quantification of parasite DNA from Babesia bovis and B. bigemina compared to standard PCR assays. A previously published cytochrome b SYBR Green qPCR was also tested in this study, showing slightly higher sensitivity than the Taqman qPCRs but requires melting curve analysis post-PCR to confirm specificity. The SYBR Green assays were further evaluated using both diagnostic submissions and vaccinated cattle (at 7, 9, 11 and 14 days post-inoculation) showed that B. bigemina can be detected more frequently than B. bovis. Due to fewer circulating parasites, B. bovis detection in carrier animals requires higher DNA input. Preliminary data for a novel fluorescent PCR genotyping based on the Internal Transcribed Spacer 1 region to detect vaccine and field alleles of B. bovis are described. This assay is capable of detecting vaccine and novel field isolate alleles in a single sample. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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4989 KiB  
Article
Pathogen and Host Response Dynamics in a Mouse Model of Borrelia hermsii Relapsing Fever
by Christopher D. Crowder, Arash Ghalyanchi Langeroudi, Azadeh Shojaee Estabragh, Eric R. G. Lewis, Renee A. Marcsisin and Alan G. Barbour
Vet. Sci. 2016, 3(3), 19; https://doi.org/10.3390/vetsci3030019 - 30 Aug 2016
Cited by 18 | Viewed by 7709
Abstract
Most Borrelia species that cause tick-borne relapsing fever utilize rodents as their natural reservoirs, and for decades laboratory-bred rodents have served as informative experimental models for the disease. However, while there has much progress in understanding the pathogenetic mechanisms, including antigenic variation, of [...] Read more.
Most Borrelia species that cause tick-borne relapsing fever utilize rodents as their natural reservoirs, and for decades laboratory-bred rodents have served as informative experimental models for the disease. However, while there has much progress in understanding the pathogenetic mechanisms, including antigenic variation, of the pathogen, the host side of the equation has been neglected. Using different approaches, we studied, in immunocompetent inbred mice, the dynamics of infection with and host responses to North American relapsing fever agent B. hermsii. The spirochete’s generation time in blood of infected mice was between 4–5 h and, after a delay, was matched in rate by the increase of specific agglutinating antibodies in response to the infection. After initiating serotype cells were cleared by antibodies, the surviving spirochetes were a different serotype and, as a population, grew more slowly. The retardation was attributable to the host response and not an inherently slower growth rate. The innate responses at infection peak and immediate aftermath were characterized by elevations of both pro-inflammatory and anti-inflammatory cytokines and chemokines. Immunodeficient mice had higher spirochete burdens and severe anemia, which was accounted for by aggregation of erythrocytes by spirochetes and their partially reversible sequestration in greatly enlarged spleens and elsewhere. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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Review

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322 KiB  
Review
Deviant Behavior: Tick-Borne Pathogens and Inflammasome Signaling
by Dana K. Shaw, Erin E. McClure, Xiaowei Wang and Joao H. F. Pedra
Vet. Sci. 2016, 3(4), 27; https://doi.org/10.3390/vetsci3040027 - 28 Sep 2016
Cited by 9 | Viewed by 6134
Abstract
In the face of an assault, host cells mount an immediate response orchestrated by innate immunity. Two of the best described innate immune signaling networks are the Toll- and the Nod-like receptor pathways. Extensive work has been done characterizing both signaling cascades with [...] Read more.
In the face of an assault, host cells mount an immediate response orchestrated by innate immunity. Two of the best described innate immune signaling networks are the Toll- and the Nod-like receptor pathways. Extensive work has been done characterizing both signaling cascades with several recent advances on the forefront of inflammasome biology. In this review, we will discuss how more commonly-studied pathogens differ from tick-transmitted microbes in the context of Nod-like receptor signaling and inflammasome formation. Because pathogens transmitted by ticks have unique characteristics, we offer the opinion that these microbes can be used to uncover novel principles of Nod-like receptor biology. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
1424 KiB  
Review
Parallelisms and Contrasts in the Diverse Ecologies of the Anaplasma phagocytophilum and Borrelia burgdorferi Complexes of Bacteria in the Far Western United States
by Nicole Stephenson and Janet Foley
Vet. Sci. 2016, 3(4), 26; https://doi.org/10.3390/vetsci3040026 - 22 Sep 2016
Cited by 11 | Viewed by 8066
Abstract
Anaplasma phagocytophilum and Borrelia burgdorferi are two tick-borne bacteria that cause disease in people and animals. For each of these bacteria, there is a complex of closely related genospecies and/or strains that are genetically distinct and have been shown through both observational and [...] Read more.
Anaplasma phagocytophilum and Borrelia burgdorferi are two tick-borne bacteria that cause disease in people and animals. For each of these bacteria, there is a complex of closely related genospecies and/or strains that are genetically distinct and have been shown through both observational and experimental studies to have different host tropisms. In this review we compare the known ecologies of these two bacterial complexes in the far western USA and find remarkable similarities, which will help us understand evolutionary histories and coadaptation among vertebrate host, tick vector, and bacteria. For both complexes, sensu stricto genospecies (those that infect humans) share a similar geographic range, are vectored mainly by ticks in the Ixodes ricinus-complex, utilize mainly white-footed mice (Peromyscus leucopus) as a reservoir in the eastern USA and tree squirrels in the far west, and tend to be generalists, infecting a wider variety of vertebrate host species. Other sensu lato genospecies within each complex are generally more specialized, occurring often in local enzootic cycles within a narrow range of vertebrate hosts and specialized vector species. We suggest that these similar ecologies may have arisen through utilization of a generalist tick species as a vector, resulting in a potentially more virulent generalist pathogen that spills over into humans, vs. utilization of a specialized tick vector on a particular vertebrate host species, promoting microbe specialization. Such tight host-vector-pathogen coupling could also facilitate high enzootic prevalence and the evolution of host immune-tolerance and bacterial avirulence. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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261 KiB  
Review
Ehrlichioses: An Important One Health Opportunity
by Tais B. Saito and David H. Walker
Vet. Sci. 2016, 3(3), 20; https://doi.org/10.3390/vetsci3030020 - 31 Aug 2016
Cited by 39 | Viewed by 9201
Abstract
Ehrlichioses are caused by obligately intracellular bacteria that are maintained subclinically in a persistently infected vertebrate host and a tick vector. The most severe life-threatening illnesses, such as human monocytotropic ehrlichiosis and heartwater, occur in incidental hosts. Ehrlichia have a developmental cycle involving [...] Read more.
Ehrlichioses are caused by obligately intracellular bacteria that are maintained subclinically in a persistently infected vertebrate host and a tick vector. The most severe life-threatening illnesses, such as human monocytotropic ehrlichiosis and heartwater, occur in incidental hosts. Ehrlichia have a developmental cycle involving an infectious, nonreplicating, dense core cell and a noninfectious, replicating reticulate cell. Ehrlichiae secrete proteins that bind to host cytoplasmic proteins and nuclear chromatin, manipulating the host cell environment to their advantage. Severe disease in immunocompetent hosts is mediated in large part by immunologic and inflammatory mechanisms, including overproduction of tumor necrosis factor α (TNF-α), which is produced by CD8 T lymphocytes, and interleukin-10 (IL-10). Immune components that contribute to control of ehrlichial infection include CD4 and CD8 T cells, natural killer (NK) cells, interferon-γ (IFN-γ), IL-12, and antibodies. Some immune components, such as TNF-α, perforin, and CD8 T cells, play both pathogenic and protective roles. In contrast with the immunocompetent host, which may die with few detectable organisms owing to the overly strong immune response, immunodeficient hosts die with overwhelming infection and large quantities of organisms in the tissues. Vaccine development is challenging because of antigenic diversity of E. ruminantium, the necessity of avoiding an immunopathologic response, and incomplete knowledge of the protective antigens. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
7388 KiB  
Review
Tick-Borne Relapsing Fever Spirochetes in the Americas
by Job E. Lopez, Aparna Krishnavahjala, Melissa N. Garcia and Sergio Bermudez
Vet. Sci. 2016, 3(3), 16; https://doi.org/10.3390/vetsci3030016 - 15 Aug 2016
Cited by 62 | Viewed by 13100
Abstract
Relapsing fever spirochetes are tick- and louse-borne pathogens that primarily afflict those in impoverished countries. Historically the pathogens have had a significant impact on public health, yet currently they are often overlooked because of the nonspecific display of disease. In this review, we [...] Read more.
Relapsing fever spirochetes are tick- and louse-borne pathogens that primarily afflict those in impoverished countries. Historically the pathogens have had a significant impact on public health, yet currently they are often overlooked because of the nonspecific display of disease. In this review, we discuss aspects of relapsing fever (RF) spirochete pathogenesis including the: (1) clinical manifestation of disease; (2) ability to diagnose pathogen exposure; (3) the pathogen’s life cycle in the tick and mammal; and (4) ecological factors contributing to the maintenance of RF spirochetes in nature. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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Graphical abstract

1523 KiB  
Review
Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection
by Pilar Alberdi, Pedro J. Espinosa, Alejandro Cabezas-Cruz and José De la Fuente
Vet. Sci. 2016, 3(3), 15; https://doi.org/10.3390/vetsci3030015 - 15 Jul 2016
Cited by 21 | Viewed by 8552
Abstract
Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different [...] Read more.
Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis and establish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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Graphical abstract

860 KiB  
Review
Travelling between Two Worlds: Complement as a Gatekeeper for an Expanded Host Range of Lyme Disease Spirochetes
by Peter Kraiczy
Vet. Sci. 2016, 3(2), 12; https://doi.org/10.3390/vetsci3020012 - 14 Jun 2016
Cited by 23 | Viewed by 7572
Abstract
Evading innate immunity is a prerequisite for pathogenic microorganisms in order to survive in their respective hosts. Concerning Lyme disease spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato group, a broad range of diverse vertebrates serve as reservoir or even [...] Read more.
Evading innate immunity is a prerequisite for pathogenic microorganisms in order to survive in their respective hosts. Concerning Lyme disease spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato group, a broad range of diverse vertebrates serve as reservoir or even as incidental hosts, including humans. The capability to infect multiple hosts implies that spirochetes have developed sophisticated means to counter the destructive effects of complement of humans and various animals. While the means by which spirochetes overcome the hosts immune defense are far from being completely understood, there is a growing body of evidence suggesting that binding of the key regulator of the alternative pathway, Factor H, plays a pivotal role for immune evasion and that Factor H is an important determinant of host specificity. This review covers (i) the contribution of complement in host-specificity and transmissibility of Lyme disease spirochetes; (ii) the involvement of borrelial-derived determinants to host specificity; (iii) the interplay of human and animal Factor H with complement-acquiring surface proteins of diverse borrelial species; and (iv) the potential role of additional animal complement proteins in the immune evasion of spirochetes. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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Other

159 KiB  
Comment
Regarding Tick-Borne Relapsing Fever in the Americas; Some Historical Aspects of a Forgotten Disease in Colombia
by Álvaro A. Faccini-Martínez and Carlos A. Botero-García
Vet. Sci. 2016, 3(4), 33; https://doi.org/10.3390/vetsci3040033 - 4 Nov 2016
Cited by 7 | Viewed by 3908
Abstract
In the first decades of the 20th century, scientific papers were published suggesting the presence of Tick-Borne Relapsing Fever in Colombia. As a contribution, we present some historical aspects referring to this topic. Full article
(This article belongs to the Special Issue Comparative Studies in Tick-Borne Diseases in Animals and Humans)
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