title: Tissue-Specific Signatures in the Transcriptional Response to Anaplasma phagocytophilum Infection of Ixodes scapularis and Ixodes ricinus Tick Cell Lines.
abstract: Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A. phagocytophilum through the demonstration of tissue-specific molecular pathways that ensure pathogen infection, development and transmission by ticks. However, little is known about the Ixodes ricinus genes and proteins involved in the response to A. phagocytophilum infection. The tick species I. scapularis and I. ricinus are evolutionarily closely related and therefore similar responses are expected in A. phagocytophilum-infected cells. However, differences may exist between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cells associated with tissue-specific signatures of these cell lines. To address this hypothesis, the transcriptional response to A. phagocytophilum infection was characterized by RNA sequencing and compared between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell lines. The transcriptional response to infection of I. scapularis ISE6 cells resembled that of tick hemocytes while the response in I. ricinus IRE/CTVM20 cells was more closely related to that reported previously in infected tick midguts. The inhibition of cell apoptosis by A. phagocytophilum appears to be a key adaptation mechanism to facilitate infection of both vertebrate and tick cells and was used to investigate further the tissue-specific response of tick cell lines to pathogen infection. The results supported a role for the intrinsic pathway in the inhibition of cell apoptosis by A. phagocytophilum infection of I. scapularis ISE6 cells. In contrast, the results in I. ricinus IRE/CTVM20 cells were similar to those obtained in tick midguts and suggested a role for the JAK/STAT pathway in the inhibition of apoptosis in tick cells infected with A. phagocytophilum. Nevertheless, tick cell lines were derived from embryonated eggs and may contain various cell populations with different morphology and behavior that could affect transcriptional response to infection. These results suggested tissue-specific signatures in I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell line response to A. phagocytophilum infection that support their use as models for the study of tick-pathogen interactions.
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-Consejo Superior de Investigaciones Científicas- Universidad de Castilla-La Mancha-Junta de Comunidades de Castilla-La Mancha Ciudad Real, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alberdi
authors.affiliation: Animal and Plant Health Agency New Haw, Surrey, UK.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mansfield
authors.affiliation: Parasitología Animal, Instituto de Recursos Naturales y Agrobiología de Salamanca (IRNASA, Consejo Superior de Investigaciones Científicas) Salamanca, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Manzano-Román
authors.affiliation: Animal and Plant Health Agency New Haw, Surrey, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cook
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-Consejo Superior de Investigaciones Científicas- Universidad de Castilla-La Mancha-Junta de Comunidades de Castilla-La Mancha Ciudad Real, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Ayllón
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-Consejo Superior de Investigaciones Científicas- Universidad de Castilla-La Mancha-Junta de Comunidades de Castilla-La Mancha Ciudad Real, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Villar
authors.affiliation: Animal and Plant Health Agency New Haw, Surrey, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Johnson
authors.affiliation: Animal and Plant Health AgencyNew Haw, Surrey, UK; Department of Clinical Infection, Microbiology and Immunology, University of LiverpoolLiverpool, UK.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fooks
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-Consejo Superior de Investigaciones Científicas- Universidad de Castilla-La Mancha-Junta de Comunidades de Castilla-La ManchaCiudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State UniversityStillwater, OK, USA.
authors.forename: José
authors.initials: J
authors.lastname: de la Fuente
mesh_terms: D041081:Anaplasma phagocytophilum / Q000472:pathogenicity*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics*; D018884:Ixodes / Q000382:microbiology*; D012313:RNA / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D012313:RNA
keywords: anaplasma; apoptosis; rickettsia; tick; tick cell line; transcriptomics