Subolesin expression in response to pathogen infection in ticks

Abstract

BackgroundTicks (Acari: Ixodidae) are vectors of pathogens worldwide that cause diseases in humans and animals. Ticks and pathogens have co-evolved molecular mechanisms that contribute to their mutual development and survival. Subolesin was discovered as a tick protective antigen and was subsequently shown to be similar in structure and function to akirins, an evolutionarily conserved group of proteins in insects and vertebrates that controls NF-kB-dependent and independent expression of innate immune response genes. The objective of this study was to investigate subolesin expression in several tick species infected with a variety of pathogens and to determine the effect of subolesin gene knockdown on pathogen infection. In the first experiment, subolesin expression was characterized in ticks experimentally infected with the cattle pathogen, Anaplasma marginale. Subolesin expression was then characterized in questing or feeding adult ticks confirmed to be infected with Anaplasma, Ehrlichia, Rickettsia, Babesia or Theileria spp. Finally, the effect of subolesin knockdown by RNA interference (RNAi) on tick infection was analyzed in Dermacentor variabilis males exposed to various pathogens by capillary feeding (CF).ResultsSubolesin expression increased with pathogen infection in the salivary glands but not in the guts of tick vector species infected with A. marginale. When analyzed in whole ticks, subolesin expression varied between tick species and in response to different pathogens. As reported previously, subolesin knockdown in D. variabilis infected with A. marginale and other tick-borne pathogens resulted in lower infection levels, while infection with Francisella tularensis increased in ticks after RNAi. When non-tick-borne pathogens were fed to ticks by CF, subolesin RNAi did not affect or resulted in lower infection levels in ticks. However, subolesin expression was upregulated in D. variabilis exposed to Escherichia coli, suggesting that although this pathogen may induce subolesin expression in ticks, silencing of this molecule reduced bacterial multiplication by a presently unknown mechanism.ConclusionsSubolesin expression in infected ticks suggested that subolesin may be functionally important for tick innate immunity to pathogens, as has been reported for the akirins. However, subolesin expression and consequently subolesin-mediated innate immunity varied with the pathogen and tick tissue. Subolesin may plays a role in tick innate immunity in the salivary glands by limiting pathogen infection levels, but activates innate immunity only for some pathogen in the guts and other tissues. In addition, these results provided additional support for the role of subolesin in other molecular pathways including those required for tissue development and function and for pathogen infection and multiplication in ticks. Consequently, RNAi experiments demonstrated that subolesin knockdown in ticks may affect pathogen infection directly by reducing tick innate immunity that results in higher infection levels and indirectl...

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

“…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).…”

“…Subolesin is a candidate tick protective antigen discovered in I. scapularis and subsequently found to be conserved in many tick species and other eukaryotes, where it is the ortholog of insect and mammalian akirins (14,(55)(56)(57)(58). 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).…”

“…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)(11)(12)(13)(14)(15)(16)(17)(18)(19)(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).…”

Understanding the biology and control of the poultry red miteDermanyssus gallinae: a review

“…Subolesin, a tick homologue of the mammalian akarin family of proteins, is associated with the upregulation of innate immunity in various tick species (Zivkovic et al, 2010) and is proposed to be a transcription factor involved in multiple cellular processes (De la Fuente et al, 2008). Harrington et al (2009) showed that immunization of chickens with recombinant Aedes albopictus subolesin increased fed PRM mortality by 31% compared to control groups, suggesting that a potential PRM subolesin orthologue may be a target for control.…”

“…RNA interference of the subolesin gene in ticks has shown varying efficacy in terms of how well ticks are able to control bacterial infections. Zivkovic et al (2010) demonstrated that RNAi knock-down of subolesin in ticks increased infection by Francisella tularensis but decreased infection by Anaplasma marginale. Whether by means of immunological repression resulting in increased bacteria loads or by affecting other PRM systems, subolesin would make an interesting target for further vaccine studies against PRM.…”