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The severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses following ex vivo stimulation of primary bursal cells.

ABSTRACT: Transcriptomics analysis reveals that severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses following ex vivo stimulation of primary bursal cells. In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated very virulent (vv) IBDV into White Leghorn chickens from inbred line W that previously had over 24% mortality, and three inbred lines (15I, C.B4 and O) that previously had 0% mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease was associated with a significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPase, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa. Primary bursal cells cultured from line W birds and stimulated ex vivo with LPS had a more rapid up-regulation of pro-inflammatory gene expression than cells from line 15I birds, and line W birds had a significantly greater percentage of KUL01+ macrophage cells in the BF than line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in line W birds causes excessive inflammation and clinical disease following IBDV infection compared to line 15I, and we suggest that pro-inflammatory pathways could be targeted to engineer more disease resistant birds in the future

ORGANISM(S): Gallus gallus

PROVIDER: GSE166026 | GEO | 2021/06/02

REPOSITORIES: GEO

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Project description:Nasal cavity is the main gateway for pathogen infection although it composed of many layers of defending barriers. Pathogens strongly willing to enter and infect from nasal cavity with the dominant form aerosol or respiratory droplets. However, the underlying mechanism of virus nasal infection and transmission are still unknown. Hence, a better understanding of this mechanism may provide insight into the pathogenesis of virus. In this study, IBDV was select as a model virus to study nasal infection and transmission for it could infect chicken from head (nasal) to tail (basal) and lead to massive destruction of bursal IgM+ B-lymphocytes. Initially, we found IBDV mostly entered and infected the interior of chicken’s nasal, where full of lymphoid tissue and easily for virus to transfer into blood. After passing nasal barriers, IBDV was subsequently transmit into blood and infected PBMCs. Following blood circulates, IBDV then infected bursal and hugely destroyed B-lymphocytes. However, the mechanism of how IBDV influenced the bursal cells, especially how virus destroyed B-lymphocytes were still unclear. With the help of single cells RNA sequence, we identified five vigorous clusters, including three immune cells types (B-cells: 64.70%, dendritic cells: 3.32% and T-cells: 6.33%) and two non-immune cell types (epithelial cells: 23.86% and fibroblast cells: 1.80% cells). Further analyses found that B-cells population were serious damaged, especially IgM+ B cells. However, the IgA+ B cells population hugely increased after IBDV infection. Interesting, we first demonstrated that basal cells and other non-immune cells in Bursa of Fabricius (BF) were the main target for IBDV infection and replication. Together, our study not only comprehensive elaborated the airborne IBDV and its transmission via intranasal route into the BF, but also explained its distribution in different immune and nonimmune cells and immunoglobulins rearrangement after immunosuppressive disorder on an age dependent infected organ.

Dataset Information

The severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses following ex vivo stimulation of primary bursal cells.

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