Early immune responses in rainbow trout liver upon viral hemorrhagic septicemia virus (VHSV) infection

PLoS One. 2014 Oct 22;9(10):e111084. doi: 10.1371/journal.pone.0111084. eCollection 2014.


Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Chemokines / genetics
  • Chemokines / metabolism
  • Female
  • Fish Diseases / immunology*
  • Fish Diseases / metabolism
  • Fish Diseases / virology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Immunity, Cellular
  • Leukocytes / immunology
  • Leukocytes / virology
  • Liver / immunology*
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Novirhabdovirus / immunology*
  • Oncorhynchus mykiss / immunology*
  • Oncorhynchus mykiss / metabolism
  • Oncorhynchus mykiss / virology
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Receptors, Pattern Recognition / genetics
  • Rhabdoviridae Infections / immunology
  • Rhabdoviridae Infections / metabolism
  • Rhabdoviridae Infections / veterinary*
  • Rhabdoviridae Infections / virology
  • Spleen / immunology
  • Spleen / pathology
  • Transcription, Genetic
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Chemokines
  • Glycoproteins
  • Receptors, Chemokine
  • Receptors, Pattern Recognition
  • Viral Proteins

Grant support

This work was supported by the European Research Council (ERC Starting Grant 2011 280469) and by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.