Expression of heat shock proteins and subolesin affects stress responses,<i>Anaplasma phagocytophilum</i>infection and questing behaviour in the tick,<i>Ixodes scapularis</i>

Busby, Ann T.; Ayllón, Nieves; Kocan, Katherine M.; Blouin, Edmour F.; Fuente, Gabriela de la; Galindo, Ruth C.; Villar, Margarita; Fuente, José de la

doi:10.1111/j.1365-2915.2011.00973.x

Cited by 77 publications

(74 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subolesin expression is induced in response to pathogen infection in ticks and plays an important role in the tick immune response to pathogen infection through the regulation of genes involved in innate immunity (14,16,56,59). As in previous experiments, subolesin mRNA levels did not change in response to A. phagocytophilum infection of ISE6 tick cells but increased in tick guts and salivary glands (12,60). However, subolesin protein levels increased in A. phagocytophilum-infected ISE6 tick cells, suggesting that posttranscriptional mechanisms affect subolesin levels in response to infection (21,61).…”

Section: Discussionsupporting

confidence: 60%

“…Subolesin knockdown resulted in higher A. phagocytophilum infection levels in ISE6 tick cells, supporting its role in the tick immune response. However, in tick guts and salivary glands, subolesin knockdown did not affect pathogen infection levels, probably due to the role of subolesin in tissue structure and development, which are required for pathogen infection (16,25,62), pointing to differences between in vitro and in vivo studies (12,21,60).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

et al. 2013

View full text Add to dashboard Cite

dAnaplasma phagocytophilum causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects gene expression in both the vertebrate host and the tick vector, Ixodes scapularis. Here, we identified new genes, including spectrin alpha chain or alpha-fodrin (CG8) and voltage-dependent anion-selective channel or mitochondrial porin (T2), that are involved in A. phagocytophilum infection/multiplication and the tick cell response to infection. The pathogen downregulated the expression of CG8 in tick salivary glands and T2 in both the gut and salivary glands to inhibit apoptosis as a mechanism to subvert host cell defenses and increase infection. In the gut, the tick response to infection through CG8 upregulation was used by the pathogen to increase infection due to the cytoskeleton rearrangement that is required for pathogen infection. These results increase our understanding of the role of tick genes during A. phagocytophilum infection and multiplication and demonstrate that the pathogen uses similar strategies to establish infection in both vertebrate and invertebrate hosts.T icks are ectoparasites of animals and humans and are considered to be the most important arthropod vector of pathogens in some regions (1). Ixodes scapularis Say (Acari: Ixodidae) is an important vector of pathogens that infect and cause disease in humans and domestic animals in the United States. Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), the focus of this study, is the causative agent of human, canine, and equine granulocytic anaplasmosis and tick-borne fever of ruminants (2, 3).A. phagocytophilum is an intracellular bacterium that infects vertebrate host neutrophils, where it multiplies within a parasitophorous vacuole, thus evading host defenses while inhibiting apoptosis and promoting cytoskeleton rearrangement for infection and multiplication (4-8). Tick-A. phagocytophilum interactions are not as well characterized as those between pathogen and vertebrate hosts (4). While A. phagocytophilum has been shown to infect I. scapularis gut cells (9) and salivary glands (10), the developmental cycle of this pathogen has not been described in ticks. Tick proteins such as Salp16, subolesin, antifreeze glycoprotein IAFGP, and alpha1-3-fucosyltransferease were differentially regulated and required for A. phagocytophilum infection of I. scapularis (10-20). Activation of heat shock proteins and other stress response proteins in ticks and cultured tick cells in response to A. phagocytophilum infection was also characterized by proteomics and transcriptomics analyses (21).The overall goal of our research is to characterize molecular interactions at the vector-pathogen interface and develop vaccines for the control of tick infestations and pathogen infection/transmission. Our hypothesis is that tick genes differentially expressed in response to pathogen infection would include those involved in pathogen infection, multiplication, and transmission, as well as in the tick protective response to infection. In this researc...

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In the study reported here, Hsp70 and Hsp90 were overrepresented in infected tick cells. The increase in Hsp levels counteracts the negative effect of heat shock and pathogen infection on tick questing behavior and increases tick survival, those playing an important role in pathogen transmission and the adaptation of tick populations to challenging environmental conditions (70,71). These results also highlight coevolutionary mechanisms by which ticks benefit from A. phagocytophilum infection by increasing survival while pathogens guarantee transmission to susceptible hosts.…”

Section: Discussionmentioning

confidence: 73%

“…Recent results have shown how ticks benefit from infection by A. phagocytophilum (69,70). Neelakanta et al (69) demonstrated that infection with A. phagocytophilum induces I. scapularis ticks to express an antifreeze glycoprotein that increases tick cold tolerance.…”

Section: Discussionmentioning

confidence: 99%

Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

Villar

Ayllón

Alberdi

et al. 2015

Molecular & Cellular Proteomics

112

190

View full text Add to dashboard Cite

Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human granulocytic anaplasmosis. These intracellular bacteria establish infection by affecting cell function in both the vertebrate host and the tick vector, Ixodes scapularis. Previous studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection. However, in the postgenomic era, the integration of omics datasets through a systems biology approach allows network-based analyses to describe the complexity and functionality of biological systems such as host-pathogen interactions and the discovery of new targets for prevention and control of infectious diseases. This study reports the first systems biology integration of metabolomics, transcriptomics, and proteomics data to characterize essential metabolic pathways involved in the tick response to A. phagocytophilum infection. The ISE6 tick cells used in this study constitute a model for hemocytes involved in pathogen infection and immune response. The results showed that infection affected protein processing in endoplasmic reticulum and glucose metabolic pathways in tick cells. These results supported tick-Anaplasma co-evolution by providing new evidence of how tick cells limit pathogen infection, while the pathogen benefits from the tick cell response to establish infection. Additionally, ticks benefit from A. phagocytophilum infection by increasing survival while pathogens guarantee transmission. The results suggested that A. phagocytophilum induces protein misfolding to limit the tick cell response and facilitate infection but requires protein degradation to prevent ER stress and cell apoptosis to survive in infected cells. Additionally, A. phagocytophilum may benefit from the tick cell's ability to limit bacterial infection through PEPCK inhibition leading to decreased glucose metabolism, which also results in the inhibition of cell apoptosis that increases infection of tick cells. These results support the use of this experimental approach to systematically identify cell pathways and molecular mechanisms involved in tick-pathogen interactions. Data are available via ProteomeXchange with identifier PXD002181. Molecular & Cellular

show abstract

“…The heat shock response is a conserved reaction of both cells and organisms to high temperatures and other stress conditions, and is effected by HSPs [41]. It has been reported that HSP20 can protect tick cells from stress, impact tick behavior such as questing speed, and can be involved in the I. scapularis protective response to A. phagocytophilum infection [42], [43]. However, these studies also reported that in the natural vector-pathogen relationship, HSPs and other stress response proteins were not strongly activated, which is likely due to tick-pathogen co-evolution [43].…”

Section: Heat Shock Proteins (Hsp) Familymentioning

confidence: 99%

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

et al. 2014

View full text Add to dashboard Cite

Ixodes ricinus is the most widespread and abundant tick in Europe, frequently bites humans, and is the vector of several pathogens including those responsible for Lyme disease, Tick-Borne Encephalitis, anaplasmosis, babesiosis and bartonellosis. These tick-borne pathogens are transmitted to vertebrate hosts via tick saliva during blood feeding, and tick salivary gland (SG) factors are likely implicated in transmission. In order to identify such tick factors, we characterized the transcriptome of female I. ricinus SGs using next generation sequencing techniques, and compared transcriptomes between Bartonella henselae-infected and non-infected ticks. High-throughput sequencing of I. ricinus SG transcriptomes led to the generation of 24,539 isotigs. Among them, 829 and 517 transcripts were either significantly up- or down-regulated respectively, in response to bacterial infection. Searches based on sequence identity showed that among the differentially expressed transcripts, 161 transcripts corresponded to nine groups of previously annotated tick SG gene families, while the others corresponded to genes of unknown function. Expression patterns of five selected genes belonging to the BPTI/Kunitz family of serine protease inhibitors, the tick salivary peptide group 1 protein, the salp15 super-family, and the arthropod defensin family, were validated by qRT-PCR. IrSPI, a member of the BPTI/Kunitz family of serine protease inhibitors, showed the highest up-regulation in SGs in response to Bartonella infection. IrSPI silencing impaired tick feeding, as well as resulted in reduced bacterial load in tick SGs. This study provides a comprehensive analysis of I. ricinus SG transcriptome and contributes significant genomic information about this important disease vector. This in-depth knowledge will enable a better understanding of the molecular interactions between ticks and tick-borne pathogens, and identifies IrSPI, a candidate to study now in detail to estimate its potentialities as vaccine against the ticks and the pathogens they transmit.

show abstract

Expression of heat shock proteins and subolesin affects stress responses,Anaplasma phagocytophiluminfection and questing behaviour in the tick,Ixodes scapularis

Cited by 77 publications

References 55 publications

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

Anaplasma phagocytophilum Inhibits Apoptosis and Promotes Cytoskeleton Rearrangement for Infection of Tick Cells

Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells*

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

Contact Info

Product

Resources

About