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Viruses2024; 16(12); doi: 10.3390/v16121804

Horse Innate Immunity in the Control of Equine Infectious Anemia Virus Infection: A Preliminary Study.

Abstract: The mechanisms of the innate immunity control of equine infectious anemia virus in horses are not yet widely described. Equine monocytes isolated from the peripheral blood of three Equine infectious anemia (EIA) seronegative horses were differentiated in vitro into macrophages that gave rise to mixed cell populations morphologically referable to M1 and M2 phenotypes. The addition of two equine recombinant cytokines and two EIA virus reference strains, Miami and Wyoming, induced a more specific cell differentiation, and as for other species, IFNγ and IL4 stimulation polarized horse macrophages respectively towards the M1 and the M2 phenotypes. Infection with EIAV reference strains resulted in a morphological transformation of macrophages compatible with the M1 differentiation pattern. All samples were also analyzed by molecular analyses for equine herpesviruses that could have acted as an interference and were found to be negative. The mRNA expression level of the pro-inflammatory genes MMP13 and IL6 in treated equine monocyte-derived macrophages (eMDMs) was evaluated by a SYBR® Green real-time PCR. In this study, MMP13 represented a reliable target gene to evaluate pro-inflammatory status of macrophages in horses because IFNγ and EIAV infection considerably increased its expression. A more in-depth study of the expression genes of both cytokine-induced and virus-induced markers of eMDM polarization may help us to understand whether these markers in horses are the same as those found in other animal species with similar pathways of innate immunity activation. The identified markers of each macrophage population would allow analysis of the differentiation profiles that could provide information on virus infectivity control in equid populations, envisioning their use in therapeutic strategies.
Publication Date: 2024-11-21 PubMed ID: 39772115PubMed Central: PMC11680308DOI: 10.3390/v16121804Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores how the innate immune system of horses might play a role in controlling an infection from the equine infectious anemia virus (EIAV). The researchers looked at how certain cells, called macrophages, changed in response to this virus.

Background and Purpose of the Study

  • The study sets out to explore the largely unknown mechanisms through which horses’ innate immunity controls EIAV infection. The researchers focused on equine macrophages, which are crucial immune cells involved in detecting, engulfing and destroying pathogens. Understanding these cellular responses may provide insights into potential therapeutic strategies against EIAV.

Methods

  • The study drew from the peripheral blood of three EIA seronegative horses. The selected monocytes – types of white blood cells – were grown in a lab setting into macrophages.
  • The researchers then exposed these macrophages to two types of EIAV strains (Miami and Wyoming), as well as two equine recombinant cytokines known to regulate immune responses. This exposure led to the macrophages differentiating into M1 and M2 phenotypes, cell types with different patterns of gene expression and function.
  • The team used molecular analysis to rule out the presence of equine herpesviruses, which could interfere with the results.
  • The researchers also examined the mRNA expression level of pro-inflammatory genes and using a SYBR Green real-time PCR, a technique to measure the amount of specific RNA sequences in a sample.

Findings and Implications

  • The study found that exposure to EIAV and certain cytokines led to morphological changes in horse macrophages, with transformations indicative of the M1 differentiation pattern. The M1 phenotype is typically associated with inflammatory responses.
  • The study also noted increased mRNA expression of pro-inflammatory genes in samples exposed to IFNγ ( a particular cytokine) and EIAV. This establishes as a reliable target gene to assess the pro-inflammatory status of horses’ macrophages.
  • The findings suggest that further research on gene expression in eMDM polarization (i.e., how macrophages differentiate) could improve the understanding of horses’ immune response mechanisms. These immune markers could potentially provide insights into viral control within horse populations and could be utilized in the development of therapeutic strategies against EIAV infection.

Cite This Article

APA
Cardeti G, Manna G, Cersini A, Nardini R, Rosati S, Reina R, Cittadini M, Sittinieri S, Altigeri A, Marcario GA, Scicluna MT. (2024). Horse Innate Immunity in the Control of Equine Infectious Anemia Virus Infection: A Preliminary Study. Viruses, 16(12). https://doi.org/10.3390/v16121804

Publication

ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 16
Issue: 12

Researcher Affiliations

Cardeti, Giusy
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Manna, Giuseppe
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Cersini, Antonella
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Nardini, Roberto
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Rosati, Sergio
  • Department of Veterinary Science, University of Turin, Largo P. Braccini 2, 10095 Torino, Italy.
Reina, Ramses
  • Instituto de Agrobiotecnología IDAB-CSIC, Av. de Pamplona, 123, Mutilva Baja, 31192 Navarra, Spain.
Cittadini, Marina
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Sittinieri, Stefania
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Altigeri, Alessia
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Marcario, Gaetana Anita
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
Scicluna, Maria Teresa
  • Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.

MeSH Terms

  • Animals
  • Horses
  • Immunity, Innate
  • Infectious Anemia Virus, Equine / immunology
  • Infectious Anemia Virus, Equine / genetics
  • Macrophages / immunology
  • Macrophages / virology
  • Equine Infectious Anemia / immunology
  • Equine Infectious Anemia / virology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Cell Differentiation
  • Monocytes / immunology
  • Monocytes / virology
  • Cells, Cultured
  • Interferon-gamma / immunology

Grant Funding

  • IZSLT 09/17 RC / Italian Ministry of Health

Conflict of Interest Statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

This article includes 19 references
  1. Crespo H, Bertolotti L, Juganaru M, Glaria I, de Andrés D, Amorena B, Rosati S, Reina R. Small Ruminant Macrophage Polarization May Play a Pivotal Role on Lentiviral Infection. Vet. Res. 2013;44:83.
    doi: 10.1186/1297-9716-44-83pmc: PMC3850683pubmed: 24070317google scholar: lookup
  2. Câmara RJF, Bueno BL, Resende CF, Balasuriya UBR, Sakamoto SM, Reis JKPD. Viral Diseases that Affect Donkeys and Mules. Animals 2020;10:2203.
    doi: 10.3390/ani10122203pmc: PMC7760297pubmed: 33255568google scholar: lookup
  3. Leroux C, Cadoreé J, Montelaro RC. Equine Infectious Anemia Virus (EIAV): What Has HIV’s Country Cousin Got to Tell us?. Vet. Res. 2004;35:485–512.
    doi: 10.1051/vetres:2004020pubmed: 15236678google scholar: lookup
  4. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677–686.
    doi: 10.1016/j.it.2004.09.015pubmed: 15530839google scholar: lookup
  5. Kedzierska K, Crowe SM. The Role of Monocytes and Macrophages in the Pathogenesis of HIV-1. Infect. Curr. Med. Chem. 2002;9:1893–1903.
    doi: 10.2174/0929867023368935pubmed: 12369874google scholar: lookup
  6. Nardini N, Autorino GL, Ricci I, Frontoso R, Rosone F, Simula M, Scicluna MT. Validation According to OIE Criteria of a Monoclonal, Recombinant p26-based, Serologic Competitive Enzyme-linked Immunosorbent Assay as Screening Method in Surveillance Programs for the Detection of Equine Infectious Anemia Antibodies. J. Vet. Diagn. Investig. 2016;28:88–97.
    doi: 10.1177/1040638715625092pubmed: 26965228google scholar: lookup
  7. EURL European Union Reference Laboratory for Equine Diseases ANSES. [(accessed on 1 May 2024)]. Available online: https://sitesv2.anses.fr/en/minisite/equine-diseases/sop.
  8. Scicluna MT, Autorino GL, Cook SJ, Issel CJ, Cook RF, Nardini R. Validation of an Immunoblot Assay Employing an Objective Reading System and Used as a Confirmatory Test in Equine Infectious Anaemia Surveillance Programs. J. Virol. Methods. 2019;266:77–88.
  9. Raabe MR, Issel CJ, Montelaro RC. Equine Monocyte-derived Macrophage Cultures and their Applications for Infectivity and Neutralization Studies of Equine Infectious Anemia Virus. J. Virol. Methods. 1998;71:87–104.
    doi: 10.1016/S0166-0934(97)00204-8pubmed: 9628225google scholar: lookup
  10. Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG. Infection of Equine Monocyte-Derived Macrophages with an Attenuated Equine Infectious Anemia Virus (EIAV) Strain Induces a Strong Resistance to the Infection by a Virulent EIAV Strain. Vet. Res. 2014;45:82.
    doi: 10.1186/s13567-014-0082-ypmc: PMC4283155pubmed: 25106750google scholar: lookup
  11. Menarim BC, Gillis KH, Oliver A, Ngo Y, Were SR, Barrett SH, Rodgerson DH, Dahlgren LA. Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints. Front. Vet. Sci. 2020;7:568756.
    doi: 10.3389/fvets.2020.568756pmc: PMC7726135pubmed: 33324696google scholar: lookup
  12. Scicluna MT, Issel CJ, Cook FR, Manna G, Cersini A, Rosone F, Frontoso R, Caprioli A, Antognetti V, Autorino GL. Is a Diagnostic System Based Exclusively on Agar Gel Immunodiffusion Adequate for Controlling the Spread of Equine Infectious Anaemia?. Vet. Microbiol. 2013;165:23–34.
    doi: 10.1016/j.vetmic.2013.02.027pubmed: 23618837google scholar: lookup
  13. Dong JB, Zhu W, Cook FR, Goto Y, Horii Y, Haga T. Development of a Nested PCR Assay to Detect Equine Infectious Anemia Proviral DNA from Peripheral Blood of Naturally Infected Horses. Arch. Virol. 2012;157:2105–2111.
    doi: 10.1007/s00705-012-1406-8pubmed: 22798044google scholar: lookup
  14. Damiani A, Ciabatti I, Lorenzetti R, Scicluna MT, Autorino GL. Development of Equine Herpesvirus Type 1 and Type 4. Proceedings of the 45th National Congress of the Italian Society of Virology (SIV); Orvieto, Italy. 19–21 September 2005; pp. 115–116.
  15. Hue HS, Fortier GD, Fortier CI, Leon AM, Richard EA, Legrand LJ, Pronost SL. Detection and Quantitation of Equid Gammaherpesviruses (EHV-2, EHV-5) in Nasal Swab Using an Accredited Standardised Quantitative PCR Method. J. Virol. Methods. 2014;198:18–25.
  16. VanDevander DR, Warrener P, Bennet L, Schultz ER, Coulter S, Garber RL, Rose TM. Detection and Analysis of Diverse Herpesviral Species by Consensus Primer PCR. J. Clin. Microbiol. 1996;34:1666–1671.
  17. Lange-Consiglio A, Perrini C, Tasquier R, Deregibus MC, Camussi G, Pascucci L, Marini MG, Corradetti B, Bizzaro D, De Vita B. Equine Amniotic Microvesicles and their Anti-Inflammatory Potential in a Tenocyte Model in Vitro. Stem Cells Dev. 2016;25:610–621.
    doi: 10.1089/scd.2015.0348pubmed: 26914245google scholar: lookup
  18. Lakritz J, Marsh AE, Cockrell M, Smith MF, Tyler JW. Characterization of Gelatinases in Bronchoalveolar Lavage Fluid and Gelatinases Produced by Alveolar Macrophages Isolated from Healthy Calves. Am. J. Vet. Res. 2004;65:163–172.
    doi: 10.2460/ajvr.2004.65.163pubmed: 14974573google scholar: lookup
  19. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression. J. Immunol. 2006;177:7303–7311.
    doi: 10.4049/jimmunol.177.10.7303pubmed: 17082649google scholar: lookup