Red Blood Cells in Antiviral Immunology


The results obtained from our group have demonstrated that rainbow trout RBCs can respond to viral infections by themselves with an innate immune response, by means of producing antiviral molecules and exerting a paracrine antiviral communication with other cells, and with a potential adaptive immune response, by means of antigen processing and presentation and complement system regulation.Fish immunology and virology.


Fish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle.

In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production.
Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity.
In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our work on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that we chose a working model composed of the rainbow trout, the viral haemorrhagic septicaemia virus (VHSV) and the glycoprotein G of VHSV (GVHSV), the antigen encoded by this DNA vaccine.



    Dr. María del Mar Ortega Villaizán-Romo

    Senior Research

    Dr. Verónica Chico Gras

    Postdoctoral Researcher

    María Elizabeth Salvador Mira

    PhD Student

    Celia García Quintanilla

    PhD Student


    Dr. Sara Puente Marín

    Graduated PhD Student

    Dr. Iván Nombela Díaz

    Graduated PhD Student

    Remedios Torres Montero

    Support Personnel

    Efrén Lucas Mañogil

    Support Personnel



    Nombela I. et al. (2019)

    Vaccines (Basel), DOI:

    Integrated Transcriptomic and Proteomic Analysis of Red Blood Cells from Rainbow Trout Challenged with VHSV Point Towards Novel Immunomodulant Targets.

    Puente-Marin S., et al. (2019)

    Vaccines (Basel), DOI:

    Potencial Role of Rainbow Trout Erytrocytes as Mediators in the Immune Response Induced by a DNA vaccine in Fish.

    puente-marin s., et al. (2019)

    Front Immunol., DOI:

    Fish Red Blood Cells Modulate Immune Genes in Response to Bacterial Inclusion Bodies Made of TNFα and a G-VHSV Fragment.

    CHICO, V., et al. (2019)

    Front Immunol., DOI:

    IFIT5 Participates in the Antiviral Mechanisms of Rainbow Trout Red Blood Cells.

    NOMBELA I., et al. (2019)

    Cells, DOI:

    Rainbow Trout Red Blood Cells Exposed to Viral Hemorrhagic Seoticemia Virus Up-Regulate Antigen-Processing Mechanisms and MHC I&II, CD86 and Antigen-presenting Cell Markers.

    JUNG MH., et al. (2019)

    Front Immunol., DOI:

    The Megalocytivirus RBIV Induces Apoptosis and MHC Class I Presentation in Rock Bream (Oplegnathus fasciatus) Red Blood Cells.

    CHICO V., et al. (2018)

    IntechOpen, DOI: 10.5772/intechopen.80545

    Nucleated Red Blood Cells Contribute to the Host Immune Response Against Pathogens, Immune Response Activation and Immunomodulation.

    Puente-Marin S., et al. (2018)

    Genes, DOI:

    In silico functional networks identified in fish nucleated red blood cells by means of transcriptomic and proteomic profiling

    Chico V., et al. (2018)

    Cells, DOI: 10.3390/cells7040031

    Shape-shifted red blood cells: a novel red blood cell stage? .

    nombela i. and ortega-villaizan M. M. (2018)

    PLOS Pathogens, DOI: 10.1371/journal.ppat.1006910

    Nucleated red blood cells: Immune cell mediators of the antiviral response.