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

Sara Puente-Marin,Rosemary Thwaite,Nerea Roher,Luis Mercado,Maria Del Mar Ortega-Villaizan,Julio Coll

doi:10.3389/fimmu.2019.01055

Abstract

Fish Red-Blood Cells (RBCs) are nucleated cells that can modulate the expression of different sets of genes in response to stimuli, playing an active role in the homeostasis of the fish immune system. Nowadays, vaccination is one of the main ways to control and prevent viral diseases in aquaculture and the development of novel vaccination approaches is a focal point in fish vaccinology. One of the strategies that has recently emerged is the use of nanostructured recombinant proteins. Nanostructured cytokines have already been shown to immunostimulate and protect fish against bacterial infections. To explore the role of RBCs in the immune response to two nanostructured recombinant proteins, TNFα and a G-VHSV protein fragment, we performed different in vitro and in vivo studies. We show for the first time that rainbow trout RBCs are able to endocytose nanostructured TNFα and G-VHSV protein fragment in vitro, despite not being phagocytic cells, and in response to nanostructured TNFα and G-VHSV fragment, the expression of different immune genes could be modulated.

Highlights

Fish red blood cells (RBCs) are nucleated cells that contain organelles in their cytoplasm unlike those of mammals [1]
inclusion bodies (IBs) uptake was confirmed by confocal 3D images, which showed the internalization of IBTNFα (Figure 2A) and IBfrg16G−viral hemorrhagic septicaemia virus (VHSV) (Figure 2B) in the cytosol of RBCs
The uptake of IBs has been reported in rainbow trout macrophages (RT-HKM) and zebrafish liver cells (ZFL)

Summary

Introduction

Fish red blood cells (RBCs) are nucleated cells that contain organelles in their cytoplasm unlike those of mammals [1]. Nucleated RBCs are able to phagocytose and act as antigen presenting cells [2, 3] They can respond to different pathogen associated molecular patterns (PAMPs), modulate leukocyte activity, release cytokine-like factors [4, 5] and lately they have been implicated in the response to viral infections [reviewed in Nombela and Ortega-Villaizan [6]].Considering all of these findings, the potential role of RBCs in the immune system of fish takes on a new, interesting perspective. One of the best strategies for preventing and controlling viral diseases in aquaculture is DNA vaccination It remains unclear which mechanisms are responsible for this protection [7]. Viral hemorrhagic septicaemia (VHS) is a lethal infectious fish disease

Methods

Results

Conclusion