Exosome-Mediated Pathogen Transmission by Arthropod Vectors

doi:10.1016/j.pt.2018.04.001

Trends in Parasitology

Volume 34, Issue 7, July 2018, Pages 549-552

https://doi.org/10.1016/j.pt.2018.04.001 Get rights and content

Recent molecular and cellular studies have highlighted a potentially important role for tick exosomes in parasite transmission. Here we summarize evolving hypotheses about the largely unknown cellular events that may take place at the tick–host–pathogen interface, focusing on a potential role for arthropod exosomes in this tripartite interaction.

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Acknowledgments

We thank the anonymous reviewers for their constructive comments, Mr Jacinto Vázquez from CDOS ([email protected]) for the graphical design of Figure 1, and Nextgenology for Editorial service. MK was supported by the ‘Centre for research of pathogenicity and virulence of parasites’ (No. CZ.02.1.01/0.0/0.0/16_019/0000759) funded by the European Regional Development Fund (ERDF) and Ministry of Education, Youth and Sport, Czech Republic (MEYS), and research at the Institute of Parasitology,

References (14)

S. Karim
RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding
Biochem. Biophys. Res. Commun.
(2005)
S. Karim
Amblyomma americanum salivary glands: double-stranded RNA-mediated gene silencing of synaptobrevin homologue and inhibition of PGE2 stimulated protein secretion
Insect Biochem. Mol. Biol.
(2004)
B.J. Tauro
Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes
Methods
(2012)
D. Koppers-Lalic
Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes
Cell Rep.
(2014)
M.R. Mugnier
Vesicles as vehicles for virulence
Trends Parasitol.
(2016)
V.D. Atayde
Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut
Cell Rep.
(2015)
J. Chmelar
Sialomes and mialomes: a systems-biology view of tick tissues and tick–host interactions
Trends Parasitol.
(2016)

There are more references available in the full text version of this article.

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A microRNA profile of the saliva in the argasid ticks Ornithodoros erraticus and Ornithodoros moubata and prediction of specific target genes
2023, Ticks and Tick-borne Diseases
Ornithodoros erraticus and Ornithodoros moubata ticks are the main vectors of the agents of human relapsing fever (TBRF) and African swine fever (ASF) in the Mediterranean Basin and Africa, respectively. Tick saliva is crucial for complete tick feeding and pathogen transmission, as it contains numerous molecules such as proteins, lipids, and non-coding RNAs (ncRNA) including microRNAs (miRNA). MiRNAs are small ncRNAs capable of regulating the expression of their target messenger RNA (mRNA) leading to degradation or inhibition of its translation into protein. Research on miRNAs from ixodid ticks has revealed that miRNAs are involved in the regulation of different physiological processes of ticks, as well as in the modulation of host gene expression, immune response to tick bite and pathogen transmission. Regarding argasid ticks, there is not information about their miRNAs or their potential involvement in tick physiology and/or in the regulation of the tick-host-pathogen interactions. The aim of this work was to profile the miRNAs expressed in the saliva of O. erraticus and O. moubata, and the in silico prediction and functional analysis of their target genes in the swine host. As a whole, up to 72 conserved miRNAs families were identified in both species: 35 of them were shared and 23 and 14 families were unique to O. erraticus and O. moubata, respectively. The most abundant miRNAs families were mir-1, mir-10 and let-7 in O. erraticus and let-7, mir-252, mir-10 in O. moubata. Four miRNAs sequences of each species were validated by RT-qPCR confirming their presence in the saliva. Target gene prediction in the host (Sus scrofa) and functional analysis showed that the selected miRNAs are mainly involved in processes related to signal transduction, regulation of mRNA transcription and gene expression, synapse regulation, immune response, angiogenesis and vascular development. These results suggest that miRNAs could play an important role at the tick-host interface, providing new insights into this complex relationship that may contribute to a more precise selection of tick molecules for the development of therapeutic and immune strategies to control tick infestations and tick-borne pathogens.
Tick extracellular vesicles in host skin immunity and pathogen transmission
2023, Trends in Parasitology
Ticks can transmit a variety of human pathogens, including intracellular and extracellular bacteria, viruses, and protozoan parasites. Historically, their saliva has been of immense interest due to its anticoagulant, anti-inflammatory, and anesthetic properties. Only recently, it was discovered that tick saliva contains extracellular vesicles (EVs). Briefly, it has been observed that proteins associated with EVs are important for multiple tick-borne intracellular microbial lifestyles. The impact of tick EVs on viral and intracellular bacterial pathogen transmission from the tick to the mammalian host has been shown experimentally. Additionally, tick EVs interact with the mammalian skin immune system at the bite site. The interplay between tick EVs, the transmission of pathogens, and the host skin immune system affords opportunities for future research.
Role of ISG15 post-translational modification in immunity against Mycobacterium tuberculosis infection
2022, Cellular Signalling
Citation Excerpt :
Therefore the ISGylation of BECN1and RIG-I may impede this pathogen-mediated autophagy. Exosome can facilitate the spread of mycobacterial proteins [105,106]. The endosomal sorting complex required for transport (ESCRT) machinery is essential for the secretion of exosomes through the fusion of multivesicular bodies (MVBs) with the cyto-plasma membrane.
ISG15 encoded by a type I interferon (IFN) inducible gene mediates an important cellular process called ISGylation. ISGylation emerges as a powerful host tactic against intracellular pathogens like Mycobacterium tuberculosis (Mtb). However, the exact role of ISGylation in immunity remains elusive. To shed light on how ISGylation, which is both interesting and complex, participates in immunity against Mtb, this manuscript summarized the current knowledge about the structural characteristics and targets of ISG15 and how ISGylation cross-talks with other host post-translational modifications to exert its effect.
miRNA profile of extracellular vesicles isolated from saliva of Haemaphysalis longicornis tick
2020, Acta Tropica
Citation Excerpt :
Presence of such molecules within the parasitic EVs suggests that vesicles could transfer these molecules to modulate host cell functions (Nawaz et al., 2019). Likewise, ticks may even facilitate pathogen transmission via extracellular vesicles in their saliva (Hackenberg and Kotsyfakis, 2018). Although proteins have been identified within tick-derived EVs, however, to the best of our knowledge, miRNAs have not been studied.
Extracellular vesicles (EVs) play a key role in host-parasite interactions. Previous studies have shown that parasites can release microRNA (miRNA) containing EVs, which can transfer their contents to host cells and regulate gene expression in recipient cells. However, a little is known about the secretion of EVs by the ticks. This study was therefore, carried out to examine the saliva of ticks for the presence of miRNA containing EVs. Vesicles were purified from saliva of partially engorged Haemaphysalis longicornis ticks. Transmission electron microscopy (TEM) was carried out to confirm that vesicles within saliva were EVs based on size and morphology. Total RNA was extracted from EVs and was analyzed by deep sequencing to determine miRNA profile. TEM analysis confirmed the presence of extracellular vesicle-like structures within tick saliva. RNA-seq analysis showed that tick-derived EVs contained small non-coding RNA populations including miRNAs. The analysis of tick-derived EVs identified 36 known miRNAs, 34 novel miRNAs and 842 novel Piwi-interacting RNAs (piRNA). The results of this study provide evidence that EVs containing miRNAs can be secreted by the ticks and suggest that vesicles could transfer these miRNAs to modulate host cell functions.
RNA virome analysis of questing ticks from Hokuriku District, Japan, and the evolutionary dynamics of tick-borne phleboviruses
2020, Ticks and Tick-borne Diseases
Citation Excerpt :
Interestingly, recent studies showed a novel mode of tick-borne flavivirus transmission by tick exosomes (Zhou et al., 2018). Furthermore, tick exosomes contain proteins or microRNA derived from ticks themselves (Hackenberg and Kotsyfakis, 2018). These findings raise the possibility that MdPV may be transmitted via host tick exosomes to other tick species by cofeeding transmission (Nuttall, 2014).
Tick-borne viruses have emerged recently in many parts of the world, and the discoveries of novel tick-borne viruses have been accelerated by the development of high-throughput sequencing technology. In this study, a cost-efficient small benchtop next-generation sequencer, the Illumina MiniSeq, was used for the RNA virome analysis of questing ticks collected from Hokuriku District, Japan, and assessed for their potential utility in a tick-borne virus surveillance system. We detected two phleboviruses [Kabuto Mountain virus (KAMV) and Okutama tick virus (OKTV)], a coltivirus [Tarumizu tick virus (TarTV)], and a novel iflavirus [Hamaphysalis flava iflavirus (HfIFV)] from tick homogenates and/or cell culture supernatants after virus isolation processes. The number of sequence reads from KAMV and TarTV markedly increased when cell culture supernatants were used, indicating a successful isolation of these viruses. In contrast, OKTV and HfIFV were detected only in tick homogenates but not from cell culture supernatants, suggesting a failure to isolate these viruses. Furthermore, we performed genomic and phylogenetic analyzes of these detected viruses. OKTV and some phleboviruses discovered recently by NGS-based methods were probably deficient in the M genome segment, which are herein proposed as M segment-deficient phlebovirus (MdPV). A phylogenetic analysis of phleboviruses, including MdPV, suggested that Uukuniemi and Kaisodi group viruses and kabutoviruses evolved from an ancestral MdPV, which provides insights into the evolutionary dynamics of phleboviruses as emerging pathogens.
Host immunogenetics in tick-borne encephalitis virus infection—The CCR5 crossroad
2019, Ticks and Tick-borne Diseases
Citation Excerpt :
Also, it is likely that host-derived exosomes may affect the TBEV infection of neuronal cells (Zhou et al., 2018). In concordance, it is already known that exosomes and other extracellular vesicles influence human-virus interactions and the course of different viral infections (Chahar et al., 2015; Ellwanger et al., 2018c; Liu et al., 2017; Anderson et al., 2018; Hackenberg and Kotsyfakis, 2018; Martelli et al., 2018; Vora et al., 2018; Wang et al., 2018; Wu et al., 2018; Yao et al., 2018). Interestingly, it is possible that some viruses explore the budding and transport machinery of exosomes to evade the immune system and promote infection (Gould et al., 2003).
The human Tick-borne encephalitis virus (TBEV) infection is a complex event encompassing factors derived from the virus itself, the vectors, the final host, and the environment as well. Classically, genetic traits stand out among the human factors that modify the susceptibility and progression of infectious diseases. However, and although this is a changing scenario, studies evaluating the genetic factors that affect the susceptibility specifically to TBEV infection and TBEV-related diseases are still scarce. There are already some interesting pieces of evidence showing that some genes and polymorphisms have a real impact on TBEV infection. Also, the inflammatory processes involving tick-human interactions began to be understood in greater detail. This review focuses on the immunogenetic and inflammatory aspects concerning tick-host interactions, TBEV infections, and tick-borne encephalitis. Of note, it has been described that polymorphisms in CD209, GSTM1, IL-10, IL-28B, MMP9, OAS2, OAS3, and TLR3 have a statistically significant impact on TBEV infection. Besides, CCR5, its ligands, and the CCR5Δ32 genetic variant seem to have a very important influence on the infection and its immune responses. Taking this information into consideration, a special discussion regarding the effects of CCR5 on TBEV infection and tick-borne encephalitis will be presented. Emerging topics (such as exosomes, evasins, and CCR5 blockers) involving immunological and inflammatory aspects of TBEV-human interactions will also be addressed. Lastly, the current picture of TBEV infection and the importance to address the TBEV-associated problems through the One Health perspective will be discussed.

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Trends in Parasitology

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Acknowledgments

References (14)

RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding

Biochem. Biophys. Res. Commun.

Amblyomma americanum salivary glands: double-stranded RNA-mediated gene silencing of synaptobrevin homologue and inhibition of PGE2 stimulated protein secretion

Insect Biochem. Mol. Biol.

Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes

Methods

Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes

Cell Rep.

Vesicles as vehicles for virulence

Trends Parasitol.

Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut

Cell Rep.

Sialomes and mialomes: a systems-biology view of tick tissues and tick–host interactions

Trends Parasitol.

Cited by (20)

A microRNA profile of the saliva in the argasid ticks Ornithodoros erraticus and Ornithodoros moubata and prediction of specific target genes

Tick extracellular vesicles in host skin immunity and pathogen transmission

Role of ISG15 post-translational modification in immunity against Mycobacterium tuberculosis infection

miRNA profile of extracellular vesicles isolated from saliva of Haemaphysalis longicornis tick

RNA virome analysis of questing ticks from Hokuriku District, Japan, and the evolutionary dynamics of tick-borne phleboviruses

Host immunogenetics in tick-borne encephalitis virus infection—The CCR5 crossroad

Trends in Parasitology

ForumExosome-Mediated Pathogen Transmission by Arthropod Vectors

Section snippets

Acknowledgments

Biochem. Biophys. Res. Commun.

Insect Biochem. Mol. Biol.

Methods

Cell Rep.

Trends Parasitol.

Cell Rep.

Trends Parasitol.

Forum
Exosome-Mediated Pathogen Transmission by Arthropod Vectors