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Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

View Article: PubMed Central - PubMed

ABSTRACT

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.

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Pathogens inhibit vector cell apoptosis by different mechanisms. After infection of tick salivary glands, A. phagocytophilum inhibit apoptosis by decreasing the expression of the pro-apoptotic genes coding for proteins such as ASK1 and Porin. Porin down-regulation is associated with the inhibition of mitochondrial Cyt c release (Ayllón et al., 2015a). In contrast, A. phagocytophilum infection does not affect Bcl-2 levels, probably because this protein but not Porin is essential for tick feeding (Ayllón et al., 2015a). A. phagocytophilum also induces ER stress in tick cells which play a role in reducing the levels of MKK that inhibits apoptosis (Villar et al., 2015a). Another interesting mechanism of A. phagocytophilum to inhibit apoptosis is the manipulation of glucose metabolism by reducing the levels of PEPCK (Villar et al., 2015a). The capacity of A. phagocytophilum to downregulate gene expression in neutrophils was associated with HDAC1 recruitment to the promoters of target genes by the ankyrin repeat protein AnkA (Garcia-Garcia et al., 2009a,b; Rennoll-Bankert et al., 2015). Tick HDAC1 is overrepresented in A. phagocytophilum-infected salivary glands and chemical inhibition of this protein decreases A. phagocytophilum burden in tick cells (Cabezas-Cruz et al., 2016). Infection of tick cells with flaviviruses results in the up-regulation of genes such as hsp70 that inhibit apoptosis (Mansfield et al., 2017). N, Nucleus; M, Mitochondria; ER, Endoplasmic Reticulum; Cyt c, Cytochrome c; ASK1, Apoptosis signal-regulating kinase 1; MKK, Mitogen-activated Protein Kinase; HDAC1, Histone Deacetylase 1; AnkA, Ankyrin A; PEPCK, Phosphoenolpyruvate Carboxykinase; FOXO, Forkhead box O; Hid, Head involution defective; JNK, Jun amino-terminal kinases; Casp, caspases. The molecules and processes represented in green are up-regulated, while those represented in red are down-regulated in response to infection. The activity of the molecules represented in blue varies in response to infection.
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Figure 4: Pathogens inhibit vector cell apoptosis by different mechanisms. After infection of tick salivary glands, A. phagocytophilum inhibit apoptosis by decreasing the expression of the pro-apoptotic genes coding for proteins such as ASK1 and Porin. Porin down-regulation is associated with the inhibition of mitochondrial Cyt c release (Ayllón et al., 2015a). In contrast, A. phagocytophilum infection does not affect Bcl-2 levels, probably because this protein but not Porin is essential for tick feeding (Ayllón et al., 2015a). A. phagocytophilum also induces ER stress in tick cells which play a role in reducing the levels of MKK that inhibits apoptosis (Villar et al., 2015a). Another interesting mechanism of A. phagocytophilum to inhibit apoptosis is the manipulation of glucose metabolism by reducing the levels of PEPCK (Villar et al., 2015a). The capacity of A. phagocytophilum to downregulate gene expression in neutrophils was associated with HDAC1 recruitment to the promoters of target genes by the ankyrin repeat protein AnkA (Garcia-Garcia et al., 2009a,b; Rennoll-Bankert et al., 2015). Tick HDAC1 is overrepresented in A. phagocytophilum-infected salivary glands and chemical inhibition of this protein decreases A. phagocytophilum burden in tick cells (Cabezas-Cruz et al., 2016). Infection of tick cells with flaviviruses results in the up-regulation of genes such as hsp70 that inhibit apoptosis (Mansfield et al., 2017). N, Nucleus; M, Mitochondria; ER, Endoplasmic Reticulum; Cyt c, Cytochrome c; ASK1, Apoptosis signal-regulating kinase 1; MKK, Mitogen-activated Protein Kinase; HDAC1, Histone Deacetylase 1; AnkA, Ankyrin A; PEPCK, Phosphoenolpyruvate Carboxykinase; FOXO, Forkhead box O; Hid, Head involution defective; JNK, Jun amino-terminal kinases; Casp, caspases. The molecules and processes represented in green are up-regulated, while those represented in red are down-regulated in response to infection. The activity of the molecules represented in blue varies in response to infection.

Mentions: However, the functional mechanisms by which these processes are affected at the vector-pathogen interface may vary between pathogen and vector species (Figure 4). The limited information available on the functional characterization of these processes in ticks and other arthropods limits the scope of the comparative analysis between different vectors. Nevertheless, recent results support that in some cases the protein function described in model insect species may be different in the evolutionarily distant ticks. Differences in vector competence may be genetically encoded by differences in the immune response pathways operating at each vector-pathogen interaction (Baxter et al., 2017). For example, Tudor-SN, a conserved component of the basic RNAi machinery with a variety of functions including immune response and gene regulation, is involved in defense against infection in Drosophila (Sabin et al., 2013) but not in ticks (Ayllón et al., 2015b). The IMD pathway is involved in protection against infection in arthropods, but recent results support the existence of two functionally distinct IMD circuits in insects and ticks (Shaw et al., 2017). Future comparative analyses between different vector species will provide additional information on the functional implication of the different biological processes in vector-pathogen interactions and vector competence (Gerold et al., 2017).


Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases
Pathogens inhibit vector cell apoptosis by different mechanisms. After infection of tick salivary glands, A. phagocytophilum inhibit apoptosis by decreasing the expression of the pro-apoptotic genes coding for proteins such as ASK1 and Porin. Porin down-regulation is associated with the inhibition of mitochondrial Cyt c release (Ayllón et al., 2015a). In contrast, A. phagocytophilum infection does not affect Bcl-2 levels, probably because this protein but not Porin is essential for tick feeding (Ayllón et al., 2015a). A. phagocytophilum also induces ER stress in tick cells which play a role in reducing the levels of MKK that inhibits apoptosis (Villar et al., 2015a). Another interesting mechanism of A. phagocytophilum to inhibit apoptosis is the manipulation of glucose metabolism by reducing the levels of PEPCK (Villar et al., 2015a). The capacity of A. phagocytophilum to downregulate gene expression in neutrophils was associated with HDAC1 recruitment to the promoters of target genes by the ankyrin repeat protein AnkA (Garcia-Garcia et al., 2009a,b; Rennoll-Bankert et al., 2015). Tick HDAC1 is overrepresented in A. phagocytophilum-infected salivary glands and chemical inhibition of this protein decreases A. phagocytophilum burden in tick cells (Cabezas-Cruz et al., 2016). Infection of tick cells with flaviviruses results in the up-regulation of genes such as hsp70 that inhibit apoptosis (Mansfield et al., 2017). N, Nucleus; M, Mitochondria; ER, Endoplasmic Reticulum; Cyt c, Cytochrome c; ASK1, Apoptosis signal-regulating kinase 1; MKK, Mitogen-activated Protein Kinase; HDAC1, Histone Deacetylase 1; AnkA, Ankyrin A; PEPCK, Phosphoenolpyruvate Carboxykinase; FOXO, Forkhead box O; Hid, Head involution defective; JNK, Jun amino-terminal kinases; Casp, caspases. The molecules and processes represented in green are up-regulated, while those represented in red are down-regulated in response to infection. The activity of the molecules represented in blue varies in response to infection.
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Figure 4: Pathogens inhibit vector cell apoptosis by different mechanisms. After infection of tick salivary glands, A. phagocytophilum inhibit apoptosis by decreasing the expression of the pro-apoptotic genes coding for proteins such as ASK1 and Porin. Porin down-regulation is associated with the inhibition of mitochondrial Cyt c release (Ayllón et al., 2015a). In contrast, A. phagocytophilum infection does not affect Bcl-2 levels, probably because this protein but not Porin is essential for tick feeding (Ayllón et al., 2015a). A. phagocytophilum also induces ER stress in tick cells which play a role in reducing the levels of MKK that inhibits apoptosis (Villar et al., 2015a). Another interesting mechanism of A. phagocytophilum to inhibit apoptosis is the manipulation of glucose metabolism by reducing the levels of PEPCK (Villar et al., 2015a). The capacity of A. phagocytophilum to downregulate gene expression in neutrophils was associated with HDAC1 recruitment to the promoters of target genes by the ankyrin repeat protein AnkA (Garcia-Garcia et al., 2009a,b; Rennoll-Bankert et al., 2015). Tick HDAC1 is overrepresented in A. phagocytophilum-infected salivary glands and chemical inhibition of this protein decreases A. phagocytophilum burden in tick cells (Cabezas-Cruz et al., 2016). Infection of tick cells with flaviviruses results in the up-regulation of genes such as hsp70 that inhibit apoptosis (Mansfield et al., 2017). N, Nucleus; M, Mitochondria; ER, Endoplasmic Reticulum; Cyt c, Cytochrome c; ASK1, Apoptosis signal-regulating kinase 1; MKK, Mitogen-activated Protein Kinase; HDAC1, Histone Deacetylase 1; AnkA, Ankyrin A; PEPCK, Phosphoenolpyruvate Carboxykinase; FOXO, Forkhead box O; Hid, Head involution defective; JNK, Jun amino-terminal kinases; Casp, caspases. The molecules and processes represented in green are up-regulated, while those represented in red are down-regulated in response to infection. The activity of the molecules represented in blue varies in response to infection.
Mentions: However, the functional mechanisms by which these processes are affected at the vector-pathogen interface may vary between pathogen and vector species (Figure 4). The limited information available on the functional characterization of these processes in ticks and other arthropods limits the scope of the comparative analysis between different vectors. Nevertheless, recent results support that in some cases the protein function described in model insect species may be different in the evolutionarily distant ticks. Differences in vector competence may be genetically encoded by differences in the immune response pathways operating at each vector-pathogen interaction (Baxter et al., 2017). For example, Tudor-SN, a conserved component of the basic RNAi machinery with a variety of functions including immune response and gene regulation, is involved in defense against infection in Drosophila (Sabin et al., 2013) but not in ticks (Ayllón et al., 2015b). The IMD pathway is involved in protection against infection in arthropods, but recent results support the existence of two functionally distinct IMD circuits in insects and ticks (Shaw et al., 2017). Future comparative analyses between different vector species will provide additional information on the functional implication of the different biological processes in vector-pathogen interactions and vector competence (Gerold et al., 2017).

View Article: PubMed Central - PubMed

ABSTRACT

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases.

No MeSH data available.


Related in: MedlinePlus