Potential Role of Macrophage Migration Inhibitory Factor in the Pathogenesis of Marek's Disease

Abstract

Introduction: Marek's disease virus (MDV) can cause malignant T-cell lymphomas and immunosuppression in chickens. Macrophage migration inhibitory factor (MIF) not only plays a critical role in inhibiting T-cell responses, but also contributes to multiple aspects of tumour progression. The aim of this study was to reveal the potential role of MIF in the pathogenesis of MDV infection.

Material and methods: MIF gene expression levels were measured by using real-time PCR. Expression was assayed at different times in chicken embryo fibroblast (CEF) cells and tissue samples of SPF chickens infected with different MDV strains and fold change was calculated by the 2^-△△CT method.

Results: The expression of MIF was significantly downregulated (p < 0.05 and FC > 2) in CEF cells infected with the very virulent MDV RB1B strain at 48 h post infection (hpi) and in the skin and spleen at 14 days post infection (dpi). The reduction of MIF expression was also found in CEF cells infected by reticuloendotheliosis virus (REV), avian leukosis virus subgroup J (ALV-J), and MDV vaccine strain CVI988 or in HD11 cells stimulated with TLR2, 3, 4, and 7 ligands. Interestingly, MIF expression decreased continuously from 7 to 28 dpi in the thymus after RB1B virus infection while it increased after CVI988 virus infection. Upregulated expression of MIF was found in CEF infected with RB1B at 96 hpi and in the spleen and skin at 21 and 28 dpi.

Conclusion: The present study revealed the different expression pattern of MIF in response to MDV infection and indicated that MIF level may be associated with MDV pathogenesis.

Keywords: Marek’s disease virus; chicken embryo fibroblasts; macrophage migration inhibitory factor; pathogenesis.

Fig. 1

MIF expression in CEF and HD11 cells. A – expression of MIF in CEF cells infected with RB1B or CVI988 strain; B – expression of MIF in chicken fibroblasts infected with REV or ALV-J; C – expression of MIF in HD11 in response to TLR2 and four stimulations; D – expression of MIF in CEF in response to TLR3 and TLR7 stimulations. The different number of asterisks (*) indicates statistically significant difference for the comparison of control (uninfected or untreated) and infected (or stimulated) transcripts at the same time point as determined by Student’s t-test. ** – P < 0.01, *** – P < 0.001. Error bars represent standard error

Fig. 2

MIF expression in chicken skin infected with RB1B or CVI988 strain. The different number of asterisks (*) indicates statistically significant difference for the comparison of control (uninfected) and infected transcripts at the same time point as determined by Student’s t-test. ** – P < 0.01. Error bars represent standard error