Modeling Modulation of the Tick Regulome in Response to  Anaplasma phagocytophilum  for the Identification of New Control Targets

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Abstract

Ticks act as vectors of pathogens affecting human and animal health worldwide, and recent research has focused on the characterization of tick-pathogen interactions using omics technologies to identify new targets for developing novel control interventions. The regulome (transcription factors-target genes interactions) plays a critical role in cell response to pathogen infection. Therefore, the application of regulomics to tick-pathogen interactions would advance our understanding of these molecular interactions and contribute to the identification of novel control targets for the prevention and control of tick infestations and tick-borne diseases. However, limited information is available on the role of tick regulome in response to pathogen infection. In this study, we applied complementary in silico approaches to modeling how Anaplasma phagocytophilum infection modulates tick vector regulome. This proof-of-concept research provided support for the use of network analysis in the study of regulome response to infection, resulting in new information on tick-pathogen interactions and potential targets for developing interventions for the control of tick infestations and pathogen transmission. Deciphering the precise nature of circuits that shape the tick regulome in response to pathogen infection is an area of research that in the future will advance our knowledge of tick-pathogen interactions, and the identification of new antigens for the control of tick infestations and pathogen infection/transmission.

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Most cited references 51

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Antioxidant responses and cellular adjustments to oxidative stress

Cristina Espinosa-Díez, Verónica Miguel, Daniela Mennerich … (2015)

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

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The prophenoloxidase-activating system in invertebrates.

Lage Cerenius, Kenneth Söderhäll (2004)

A major innate defense system in invertebrates is the melanization of pathogens and damaged tissues. This important process is controlled by the enzyme phenoloxidase (PO) that in turn is regulated in a highly elaborate manner for avoiding unnecessary production of highly toxic and reactive compounds. Recent progress, especially in arthropods, in the elucidation of mechanisms controlling the activation of zymogenic proPO into active PO by a cascade of serine proteinases and other factors is reviewed. The proPO-activating system (proPO system) is triggered by the presence of minute amounts of compounds of microbial origins, such as beta-1,3-glucans, lipopolysaccharides, and peptidoglycans, which ensures that the system will become active in the presence of potential pathogens. The presence of specific proteinase inhibitors prevents superfluous activation. Concomitant with proPO activation, many other immune reactions will be produced, such as the generation of factors with anti-microbial, cytotoxic, opsonic, or encapsulation-promoting activities.

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Interest in tick-borne pathogens has been enhanced by the emergence of Lyme disease and, more recently, human and animal ehrlichioses. In order to facilitate investigations of the vector phase of tick-borne disease agents in vitro, several new cell lines derived from embryonated eggs of northern (IDE lines) and southern (ISE lines) populations of the tick Ixodes scapularis were developed. The establishment and characteristics of 4 IDE (IDE1, 2, 8, and 12) and 2 ISE (ISE5 and 18) lines were described. Primary cultures were initiated in L-15B medium at 31 C from a single egg mass each and established lines developed a morphologically distinct phenotype. Myoblasts were present during the first year after isolation in several lines as isolated clusters or sheets covering the whole flask. Cell line extracts resolved by isoelectric focusing were characterized for 3 isozymes (lactate dehydrogenase, malate dehydrogenase, and malic enzyme). The combined banding patterns allowed discrimination between Ixodes cell lines and a Rhipicephalus appendiculatus cell line. Two lines, i.e., ISE5 and ISE18, had unique isozyme bands. Chromosome numbers and morphology conformed to those described from tissue squashes of I. scapularis.

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Author and article information

Contributors

Agustín Estrada-Peña: URI : http://loop.frontiersin.org/people/48840/overview

Alejandro Cabezas-Cruz: URI : http://loop.frontiersin.org/people/181573/overview

Pilar Alberdi: URI : http://loop.frontiersin.org/people/91332/overview

Margarita Villar: URI : http://loop.frontiersin.org/people/296192/overview

José de la Fuente: URI : http://loop.frontiersin.org/people/42307/overview

Journal

Journal ID (nlm-ta): Front Physiol

Journal ID (iso-abbrev): Front Physiol

Journal ID (publisher-id): Front. Physiol.

Title: Frontiers in Physiology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-042X

Publication date (Electronic): 18 April 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 462

Affiliations

[1] ¹SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM , Ciudad Real, Spain

[2] ²Facultad de Veterinaria, Universidad de Zaragoza , Zaragoza, Spain

[3] ³UMR BIPAR, INRA, ANSES, Ecole Nationale Vétérinaire d’Alfort, Université Paris-Est , Maisons-Alfort, France

[4] ⁴Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University , Stillwater, OK, United States

Author notes

Edited by: Abid Ali, Abdul Wali Khan University Mardan, Pakistan

Reviewed by: Shahid Karim, University of Southern Mississippi, United States; Snorre Stuen, Norwegian School of Veterinary Science, Norway

*Correspondence: José de la Fuente, jose_delafuente@ 123456yahoo.com

^†These authors have contributed equally to this work

This article was submitted to Invertebrate Physiology, a section of the journal Frontiers in Physiology

Article

DOI: 10.3389/fphys.2019.00462

PMC ID: 6482211

PubMed ID: 31057429

SO-VID: 2b548bae-b15d-42ba-8010-8478e0acf568

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 21 February 2019

Date accepted : 04 April 2019

Page count

Figures: 4, Tables: 0, Equations: 0, References: 61, Pages: 11, Words: 0

Funding

Funded by: Ministerio de Economía, Industria y Competitividad, Gobierno de España 10.13039/501100010198

Funded by: Universidad de Castilla-La Mancha 10.13039/501100007480

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Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets

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Abstract

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Ticks and tick-borne pathogens

Most cited references 51

Antioxidant responses and cellular adjustments to oxidative stress

The prophenoloxidase-activating system in invertebrates.

Establishment, maintenance and description of cell lines from the tick Ixodes scapularis.

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