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. 2022 Nov 13;11(11):1340.
doi: 10.3390/pathogens11111340.

The Role of Dendritic Cells in the Host Response to Marek's Disease Virus (MDV) as Shown by Transcriptomic Analysis of Susceptible and Resistant Birds

Pankaj Chakraborty  1   2 , Richard I Kuo  1   3 , Zhou Wu  1 , Katrina M Morris  1 , Bernadette M Dutia  1 , Pete Kaiser  1 , Jacqueline Smith  1
Affiliations

The Role of Dendritic Cells in the Host Response to Marek's Disease Virus (MDV) as Shown by Transcriptomic Analysis of Susceptible and Resistant Birds

Pankaj Chakraborty et al. Pathogens. .

Abstract

Despite the successful control of highly contagious tumorigenic Marek's disease (MD) by vaccination, a continuous increase in MD virus (MDV) virulence over recent decades has put emphasis on the development of more MD-resistant chickens. The cell types and genes involved in resistance therefore need to be recognized. The virus is primarily lymphotropic, but research should also focus on innate immunity, as innate immune cells are among the first to encounter MDV. Our previous study on MDV-macrophage interaction revealed significant differences between MHC-congenic lines 61 (MD-resistant) and 72 (MD-susceptible). To investigate the role of dendritic cells (DCs) in MD resistance, bone-marrow-derived DCs from these lines were infected with MDV in vitro. They were then characterized by cell sorting, and the respective transcriptomes analysed by RNA-seq. The differential expression (DE) of genes revealed a strong immune activation in DCs of the susceptible line, although an inherent immune supremacy was shown by the resistant line, including a significant expression of tumour-suppressor miRNA, gga-mir-124a, in line 61 control birds. Enrichment analysis of DE genes revealed high expression of an oncogenic transcription factor, AP-1, in the susceptible line following MDV challenge. This research highlights genes and pathways that may play a role in DCs in determining resistance or susceptibility to MDV infection.

Keywords: AP-1; Marek’s disease virus; RNAseq; chicken; dendritic cells; disease resistance; mir-124a; transcriptome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The in vitro infection of DCs from two inbred lines with Marek’s disease virus (MDV). Chicken bone-marrow-derived DCs (BMDCs) from lines 61 and 72 were cultured with chIL-4 and colony stimulating factor 2 (chCSF-2) for 4 days. On the day of infection, pre-sorted eGFP+CD45- chicken embryo fibroblasts (CEFs) were co-cultured with BMDCs at a ratio of 1:2.5 (CEF:BMDC). At 1 dpi, in vitro-infected BMDCs were characterized by FACS for the expression of eGFP and CD45. Data shown are the average percentage of infection of four independent experiments. Distribution of cells: Q1, infected CEFs; Q2, infected BMDCs; Q3, uninfected CEFs; Q4, uninfected BMDCs. (B) Graph showing means and respective standard errors of the mean (SEM) of the percentages of infected cells found within the four biological replicates from lines 61 and 72 BMDCs during cell-sorting experiments.
Figure 2
Figure 2
Venn diagram showing the overlap of differentially expressed genes between lines 61 and 72 after infection by MDV. Numbers of genes up- and downregulated are indicated.
Figure 3
Figure 3
Comparison of canonical pathways represented by genes expressed in BMDCs at inherently different levels in the two lines studied. Orange colour denotes upregulation in the MD-susceptible line (72) and blue colour represents upregulation in the MD-resistant line (61). Arrows indicate some of the pathways showing notable basal differential gene expression in each line.
Figure 4
Figure 4
A comparison of pathways activated/inhibited in lines 61 and 72 in response to MDV challenge.
See this image and copyright information in PMC

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