scholarly journals Induced Transient Immune Tolerance in Ticks and Vertebrate Host: A Keystone of Tick-Borne Diseases?

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathalie Boulanger ◽  
Stephen Wikel
Keyword(s):  
Immune Tolerance ◽  
Pathogen Transmission ◽  
Bioactive Molecules ◽  
Vertebrate Host ◽  
Infectious Agents ◽  
Global Public Health ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Immune Defenses ◽  
Tick Infection

Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission.

Tick immunobiology

Parasitology ◽  
2004 ◽  
Vol 129 (S1) ◽  
pp. S161-S176 ◽  
Author(s):  
M. BROSSARD ◽  
S. K. WIKEL
Keyword(s):  
Pathogen Transmission ◽  
Infectious Agents ◽  
Public Health Importance ◽  
Tick Saliva ◽  
Host Immune Responses ◽  
Immune Defenses ◽  
Vertebrate Hosts ◽  
And Control ◽  
Relationship Of ◽  
Immune Defences

Ticks are of vast medical and veterinary public health importance due to direct damage caused by feeding and their roles in transmitting well known and emerging infectious agents. Ticks and tick-borne pathogens stimulate the immune system of the host. Those immune interactions are of importance in tick biology, pathogen transmission and control of ticks and tick-borne diseases. Both innate and specific acquired immune defenses are involved in the responses of vertebrate hosts to infestation. Ticks have evolved countermeasures to circumvent host immune defenses. This review addresses the immunobiology of the tick–host interface from the perspectives of the pharmacology of tick saliva; relationship of tick saliva to pathogen transmission; host immune responses to infestation; tick modulation of host immune defences; and genomic/proteomic strategies for studying tick salivary gland molecules.

scholarly journals Changing the Recipe: Pathogen Directed Changes in Tick Saliva Components

2021 ◽  
Vol 18 (4) ◽  
pp. 1806
Author(s):  
Michael Pham ◽  
Jacob Underwood ◽  
Adela S. Oliva Chávez
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Encephalitis Virus ◽  
Bioactive Molecules ◽  
Tick Saliva ◽  
Tick Infection ◽  
Tick Borne Encephalitis ◽  
Pathogen Challenge ◽  
Tick Borne Encephalitis Virus ◽  
Pharmacologically Active

Ticks are obligate hematophagous parasites and are important vectors of a wide variety of pathogens. These pathogens include spirochetes in the genus Borrelia that cause Lyme disease, rickettsial pathogens, and tick-borne encephalitis virus, among others. Due to their prolonged feeding period of up to two weeks, hard ticks must counteract vertebrate host defense reactions in order to survive and reproduce. To overcome host defense mechanisms, ticks have evolved a large number of pharmacologically active molecules that are secreted in their saliva, which inhibits or modulates host immune defenses and wound healing responses upon injection into the bite site. These bioactive molecules in tick saliva can create a privileged environment in the host’s skin that tick-borne pathogens take advantage of. In fact, evidence is accumulating that tick-transmitted pathogens manipulate tick saliva composition to enhance their own survival, transmission, and evasion of host defenses. We review what is known about specific and functionally characterized tick saliva molecules in the context of tick infection with the genus Borrelia, the intracellular pathogen Anaplasma phagocytophilum, and tick-borne encephalitis virus. Additionally, we review studies analyzing sialome-level responses to pathogen challenge.

Roles of neutrophil β2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in mice

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3257-3264 ◽  
Author(s):  
Dori L. Borjesson ◽  
Scott I. Simon ◽  
Emir Hodzic ◽  
Hilde E. V. DeCock ◽  
Christie M. Ballantyne ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Etiologic Agent ◽  
Pathogen Transmission ◽  
Mouse Strains ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Knock Out ◽  
Feeding Site ◽  
Β2 Integrin ◽  
Β2 Integrins

AbstractTick saliva contains anti-inflammatory and immunosuppressive substances that facilitate blood feeding and enhance tick-vectored pathogen transmission, including Anaplasma phagocytophila,an etiologic agent of granulocytic ehrlichiosis. As such, inflammation at a tick-feeding site is strikingly different than that typically observed at other sites of inflammation. Up-regulation of CD11b/CD18 occurs in host granulocytes following interaction or infection withA phagocytophila, and the absence of CD11b/CD18 results in early increases in bacteremia. We hypothesized that β2 integrin–dependent infection kinetics and leukocyte extravasation are important determinants of neutrophil trafficking to, and pathogen acquisition at, tick-feeding sites.A phagocytophila infection kinetics were evaluated in CD11a/CD18, CD11b/CD18, and CD18 knock-out mice using quantitative polymerase chain reaction (PCR) of blood, ticks, and skin biopsies in conjunction with histopathology. A marked increase in the rate ofA phagocytophila infection of neutrophils and pathogen burden in blood followed tick feeding. Infection kinetics were modified by β2 integrin expression and systemic neutrophil counts. Significant neutrophil-pathogen trafficking was observed to both suture and tick sites. Despite the prominent role for β2 integrins in neutrophil arrest in flowing blood, successful pathogen acquisition by ticks occurred in the absence of β2 integrins. Establishment of feeding pools that rely less on leukocyte trafficking and more on small hemorrhages may explain the ready amplification of A phagocytophila DNA from ticks infested on CD11/CD18-deficient mouse strains.

Tick–host interactions: saliva-activated transmission

Parasitology ◽  
2004 ◽  
Vol 129 (S1) ◽  
pp. S177-S189 ◽  
Author(s):  
P. A. NUTTALL ◽  
M. LABUDA
Keyword(s):  
Host Species ◽  
Host Response ◽  
Pathogen Transmission ◽  
Vertebrate Host ◽  
Vector Species ◽  
Tick Saliva ◽  
Skin Site ◽  
Host Interactions ◽  
Tick Vector ◽  
Pharmacologically Active

The skin site at which ticks attach to their hosts to feed is the critical interface between the tick and its host, and tick-borne pathogens. This site is highly modified by the pharmacologically active molecules secreted in tick saliva. For pathogens, it is an ecologically privileged niche that many exploit. Such exploitation is referred to as saliva-activated transmission (SAT) – the indirect promotion of tick-borne pathogen transmission via the actions of bioactive tick saliva molecules on the vertebrate host. Here we review evidence for SAT and consider what are the most likely candidates for SAT factors among the tick pharmacopoeia of anti-haemostatic, anti-inflammatory and immunomodulatory molecules identified to date. SAT factors appear to differ for different pathogens and tick vector species, and possibly even depend on the vertebrate host species. Most likely we are searching for a suite of molecules that act together to overcome the redundancy in host response mechanisms. Whatever they turn out to be, the quest to identify the tick molecules that mediate SAT is an exciting one, and offers new insights to controlling ticks and tick-borne diseases.

scholarly journals The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 148 ◽  
Author(s):  
Adrien Blisnick ◽  
Ladislav Šimo ◽  
Catherine Grillon ◽  
Fabienne Fasani ◽  
Sébastien Brûlé ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Ixodes Ricinus ◽  
Serine Protease Inhibitor ◽  
Blood Feeding ◽  
Immunomodulatory Activity ◽  
Hard Tick ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Elastase Inhibitor

Ticks are the most important vectors of pathogens affecting both domestic and wild animals worldwide. Hard tick feeding is a slow process—taking up to several days—and necessitates extended control over the host response. The success of the feeding process depends upon injection of tick saliva, which not only controls host hemostasis and wound healing, but also subverts the host immune response to avoid tick rejection that creates a favorable niche for the survival and propagation of diverse tick-borne pathogens. Here, we report on the molecular and biochemical features and functions of an Ixodes ricinus serine protease inhibitor (IrSPI). We characterize IrSPI as a Kunitz elastase inhibitor that is overexpressed in several tick organs—especially salivary glands—during blood-feeding. We also demonstrated that when IrSPI is injected into the host through saliva, it had no impact on tissue factor pathway-induced coagulation, fibrinolysis, endothelial cell angiogenesis or apoptosis, but the protein exhibits immunomodulatory activity. In particular, IrSPI represses proliferation of CD4+ T lymphocytes and proinflammatory cytokine secretion from both splenocytes and macrophages. Our study contributes valuable knowledge to tick-host interactions and provides insights that could be further exploited to design anti-tick vaccines targeting this immunomodulator implicated in I. ricinus feeding.

scholarly journals Spotted Fever GroupRickettsiaInfection and Transmission Dynamics inAmblyomma maculatum

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Chanakan Suwanbongkot ◽  
Ingeborg M. Langohr ◽  
Emma K. Harris ◽  
Wellesley Dittmar ◽  
Rebecca C. Christofferson ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Spotted Fever ◽  
Attachment Site ◽  
Spotted Fever Group ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Content Type ◽  
Feeding Site ◽  
Vertebrate Hosts ◽  
Tick Salivary Glands

ABSTRACTTick vectors are capable of transmitting several rickettsial species to vertebrate hosts, resulting in various levels of disease. Studies have demonstrated the transmissibility of both rickettsial pathogens and novelRickettsiaspecies or strains with unknown pathogenicity to vertebrate hosts during tick blood meal acquisition; however, the quantitative nature of transmission remains unknown. We tested the hypothesis that if infection severity is a function of the rickettsial load delivered during tick transmission, then a more virulent spotted fever group (SFG)Rickettsiaspecies is transmitted at higher levels during tick feeding. UsingAmblyomma maculatumcohorts infected withRickettsia parkerior “CandidatusRickettsia andeanae,” a quantitative PCR (qPCR) assay was employed to quantify rickettsiae in tick salivary glands and saliva, as well as in the vertebrate hosts at the tick attachment site over the duration of tick feeding. Significantly greater numbers ofR. parkerithan of “Ca. Rickettsia andeanae” rickettsiae were present in tick saliva and salivary glands and in the vertebrate hosts at the feeding site during tick feeding. Microscopy demonstrated the presence of both rickettsial species in tick salivary glands, and immunohistochemical analysis of the attachment site identified localizedR. parkeri, but not “Ca. Rickettsia andeanae,” in the vertebrate host. Lesions were also distinct and more severe in vertebrate hosts exposed toR. parkerithan in those exposed to “Ca. Rickettsia andeanae.” The specific factors that contribute to the generation of a sustained rickettsial infection and subsequent disease have yet to be elucidated, but the results of this study suggest that the rickettsial load in ticks and during transmission may be an important element.

scholarly journals In silico target network analysis of de novo-discovered, tick saliva-specific microRNAs reveals important combinatorial effects in their interference with vertebrate host physiology

RNA ◽  
2017 ◽  
Vol 23 (8) ◽  
pp. 1259-1269 ◽  
Author(s):  
Michael Hackenberg ◽  
David Langenberger ◽  
Alexandra Schwarz ◽  
Jan Erhart ◽  
Michail Kotsyfakis
Keyword(s):  
Network Analysis ◽  
In Silico ◽  
De Novo ◽  
Vertebrate Host ◽  
Tick Saliva ◽  
Target Network ◽  
Host Physiology

scholarly journals Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack

2021 ◽  
Vol 11 ◽  
Author(s):  
Surendra Raj Sharma ◽  
Shahid Karim
Keyword(s):  
Tick Species ◽  
Blood Feeding ◽  
Specific Ige ◽  
Amblyomma Americanum ◽  
Bioactive Molecules ◽  
Tick Bites ◽  
Tick Saliva ◽  
Health Concerns ◽  
Novel Treatments ◽  
Significant Public Health

Ticks and tick-borne diseases are significant public health concerns. Bioactive molecules in tick saliva facilitate prolonged blood-feeding and transmission of tick-borne pathogens to the vertebrate host. Alpha-gal syndrome (AGS), a newly reported food allergy, is believed to be induced by saliva proteins decorated with a sugar molecule, the oligosaccharide galactose-⍺-1,3-galactose (α-gal). This syndrome is characterized by an IgE antibody-directed hypersensitivity against α-gal. The α-gal antigen was discovered in the salivary glands and saliva of various tick species including, the Lone Star tick (Amblyomma americanum). The underlying immune mechanisms linking tick bites with α-gal-specific IgE production are poorly understood and are crucial to identify and establish novel treatments for this disease. This article reviews the current understanding of AGS and its involvement with tick species.

scholarly journals A proteomics informed by transcriptomics insight into the proteome of Ornithodoros erraticus adult tick saliva

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Ricardo Pérez-Sánchez ◽  
Angel Carnero-Morán ◽  
M. Luz Valero ◽  
Ana Oleaga
Keyword(s):  
Mass Spectrometry ◽  
Protease Inhibitors ◽  
Model Organism ◽  
African Swine Fever ◽  
Heme Iron ◽  
Reference Database ◽  
Host Feeding ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Proteomics Informed By Transcriptomics

Abstract Background The argasid tick Ornithodoros erraticus is the main vector of tick-borne human relapsing fever (TBRF) and African swine fever (ASF) in the Mediterranean Basin. The prevention and control of these diseases would greatly benefit from the elimination of O. erraticus populations, and anti-tick vaccines are envisaged as an effective and sustainable alternative to chemical acaricide usage for tick control. Ornithodoros erraticus saliva contains bioactive proteins that play essential functions in tick feeding and host defence modulation, which may contribute to host infection by tick-borne pathogens. Hence, these proteins could be candidate antigen targets for the development of vaccines aimed at the control and prevention of O. erraticus infestations and the diseases this tick transmits. The objective of the present work was to obtain and characterise the proteome of the saliva of O. erraticus adult ticks as a means to identify and select novel salivary antigen targets. Methods A proteomics informed by transcriptomics (PIT) approach was applied to analyse samples of female and male saliva separately using the previously obtained O. erraticus sialotranscriptome as a reference database and two different mass spectrometry techniques, namely liquid chromatography–tandem mass spectrometry (LC–MS/MS) in data-dependent acquisition mode and sequential window acquisition of all theoretical fragment ion spectra MS (SWATH-MS). Results Up to 264 and 263 proteins were identified by LC–MS/MS in the saliva of O. erraticus female and male ticks, respectively, totalling 387 non-redundant proteins. Of these, 224 were further quantified by SWATH-MS in the saliva of both male and female ticks. Quantified proteins were classified into 23 functional categories and their abundance compared between sexes. Heme/iron-binding proteins, protease inhibitors, proteases, lipocalins and immune-related proteins were the categories most abundantly expressed in females, while glycolytic enzymes, protease inhibitors and lipocalins were the most abundantly expressed in males. Ninety-seven proteins were differentially expressed between the sexes, of which 37 and 60 were overexpressed in females and males, respectively. Conclusions The PIT approach demonstrated its usefulness for proteomics studies of O. erraticus, a non-model organism without genomic sequences available, allowing the publication of the first comprehensive proteome of the saliva of O. erraticus reported to date. These findings confirm important quantitative differences between sexes in the O. erraticus saliva proteome, unveil novel salivary proteins and functions at the tick–host feeding interface and improve our understanding of the physiology of feeding in O. erraticus ticks. The integration of O. erraticus sialoproteomic and sialotranscriptomic data will drive a more rational selection of salivary candidates as antigen targets for the development of vaccines aimed at the control of O. erraticus infestations and the diseases it transmits. Graphical Abstract

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