title: Systems biology of tissue-specific response to Anaplasma phagocytophilum reveals differentiated apoptosis in the tick vector Ixodes scapularis.
abstract: Anaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis nymphs and adult female midguts and salivary glands infected with A. phagocytophilum using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells. The results showed tissue-specific differences in tick response to infection and revealed differentiated regulation of apoptosis pathways. The impact of bacterial infection was more pronounced in tick nymphs and midguts than in salivary glands, probably reflecting bacterial developmental cycle. All apoptosis pathways described in other organisms were identified in I. scapularis, except for the absence of the Perforin ortholog. Functional characterization using RNA interference showed that Porin knockdown significantly increases tick colonization by A. phagocytophilum. Infection with A. phagocytophilum produced complex tissue-specific alterations in transcript and protein levels. In tick nymphs, the results suggested a possible effect of bacterial infection on the inhibition of tick immune response. In tick midguts, the results suggested that A. phagocytophilum infection inhibited cell apoptosis to facilitate and establish infection through up-regulation of the JAK/STAT pathway. Bacterial infection inhibited the intrinsic apoptosis pathway in tick salivary glands by down-regulating Porin expression that resulted in the inhibition of Cytochrome c release as the anti-apoptotic mechanism to facilitate bacterial infection. However, tick salivary glands may promote apoptosis to limit bacterial infection through induction of the extrinsic apoptosis pathway. These dynamic changes in response to A. phagocytophilum in I. scapularis tissue-specific transcriptome and proteome demonstrated the complexity of the tick response to infection and will contribute to characterize gene regulation in ticks.
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors: Nieves
authors: N
authors: Ayllón
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors: Margarita
authors: M
authors: Villar
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors: Ruth C
authors: RC
authors: Galindo
authors: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors: Katherine M
authors: KM
authors: Kocan
authors: Institute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, České Budějovice, The Czech Republic.
authors: Radek
authors: R
authors: Šíma
authors: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors: Juan A
authors: JA
authors: López
authors: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors: Jesús
authors: J
authors: Vázquez
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors: Pilar
authors: P
authors: Alberdi
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Center for Infection and Immunity of Lille (CIIL), Université Lille Nord de France, Institut Pasteur de Lille, Lille, France.
authors: Alejandro
authors: A
authors: Cabezas-Cruz
authors: Institute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, České Budějovice, The Czech Republic.
authors: Petr
authors: P
authors: Kopáček
authors: SaBio. Instituto de Investigación en Recursos Cinegéticos IREC, CSIC-UCLM-JCCM, Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors: José
authors: J
authors: de la Fuente
mesh_terms: D041081:Anaplasma phagocytophilum / Q000235:genetics* / Q000472:pathogenicity; D000712:Anaplasmosis / Q000235:genetics* / Q000382:microbiology / Q000635:transmission; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007303:Insect Vectors / Q000235:genetics / Q000382:microbiology; D018884:Ixodes / Q000382:microbiology; D009928:Organ Specificity; D034622:RNA Interference; D012469:Salivary Glands / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000235:genetics; D049490:Systems Biology; D059467:Transcriptome / Q000235:genetics