Atrophy of primary lymphoid organs induced by Marek\u2019s disease virus during early infection is associated with increased apoptosis, inhibition of cell proliferation and a severe B-lymphopenia

Camille Berthault,Sonja Härtle,Thibaut Larcher,Jean-François Vautherot,Caroline Denesvre,Laetitia Trapp-Fragnet

doi:10.1186/s13567-018-0526-x

Camille Berthault, Sonja Härtle + Show 4 more

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https://doi.org/10.1186/s13567-018-0526-x

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Abstract

Marek’s disease is a multi-faceted highly contagious disease affecting chickens caused by the Marek’s disease alphaherpesvirus (MDV). MDV early infection induces a transient immunosuppression, which is associated with thymus and bursa of Fabricius atrophy. Little is known about the cellular processes involved in primary lymphoid organ atrophy. Here, by in situ TUNEL assay, we demonstrate that MDV infection results in a high level of apoptosis in the thymus and bursa of Fabricius, which is concomitant to the MDV lytic cycle. Interestingly, we observed that in the thymus most of the MDV infected cells at 6 days post-infection (dpi) were apoptotic, whereas in the bursa of Fabricius most of the apoptotic cells were uninfected suggesting that MDV triggers apoptosis by two different modes in these two primary lymphoid organs. In addition, a high decrease of cell proliferation was observed from 6 to 14 dpi in the bursa of Fabricius follicles, and not in the thymus. Finally, with an adapted absolute blood lymphocyte count, we demonstrate a major B-lymphopenia during the two 1st weeks of infection, and propose this method as a potent non-invasive tool to diagnose MDV bursa of Fabricius infection and atrophy. Our results demonstrate that the thymus and bursa of Fabricius atrophies are related to different cell mechanisms, with different temporalities, that affect infected and uninfected cells.

Highlights

Marek’s disease (MD) is a major disease of poultry, with an estimated annual cost of 1–2 billions of dollars [1]
Marek’s disease alphaherpesvirus (MDV) induces a severe atrophy of the thymus and of the bursa at early time points post‐infection To verify the intensity and kinetics of MDV-induced thymus and bursa atrophy in our in vivo experimental model, we injected vvRB-1B MDV-infected chicken embryonic skin cells (CESC) (MDV group) or uninfected CESC (CTL group) intramuscularly in 2-day-old White Leghorn B19/B19 chicks
We detected a significant atrophy of the thymus and of the bursa in the MDV group compared to the control group at 6 and 10 dpi respectively (29% in the thymus at 6 dpi; 44% for the thymus and 39% for the bursa at 10 dpi) (Figure 1A)

Summary

Introduction

Marek’s disease (MD) is a major disease of poultry, with an estimated annual cost of 1–2 billions of dollars [1]. Marek’s disease Virus (MDV) (or Gallid herpesvirus type 2), caused by the highly contagious alphaherpesvirus, is mostly recognized for lethal T cell lymphoma and immunosuppression [2,3,4]. Upon entry via the respiratory tract, MDV is transported to the major lymphoid organs of birds MDV early infection is associated with an early and transient atrophy of the bursa and thymus, which is more or less severe depending on the virulence of the strain [16]. The atrophy is accompanied by major histological lesions, a loss of thymic cortical cells and a degeneration of bursa follicles [17, 18]. The thymus and bursa are the primary lymphoid organs of chickens, where T- and B-cells undergo development, respectively. Differentiated T-cells are detectable out of the thymus in the embryo from stages E15–E16 [19] and B-cells expressing IgM start to emigrate out of the bursa around hatching [20]

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