Differential modulation of cytokine, chemokine and Toll like receptor expression in chickens infected with classical and variant infectious bursal disease virus

Abstract

Infectious bursal disease (IBD) is an important immunosuppressive disease of chickens. The causative agent, infectious bursal disease virus (IBDV), consists of two serotypes, 1 and 2. Serotype 1 consists of classic IBDV (cIBDV) and variant IBDV (vIBDV). Both of these strains vary in antigenicity and pathogenesis. The goal of this study was to compare the immunopathogenesis of cIBDV and vIBDV. Three-week-old specific pathogen free chickens were inoculated intraocularly with standard challenge strain (STC) (cIBDV) and a variant strain Indiana (IN) (vIBDV). The cIBDV produced more pronounced bursal damage, inflammatory response and infiltration of T cells as compared to vIBDV. There were significant differences in the expression of innate (IFN-α and IFN-β), proinflammatory cytokine and mediator (IL-6 and iNOS) in cIBDV- and vIBDV-infected bursas. The expression of chemokines genes, IL-8 and MIP-α was also higher in cIBDV-infected chickens during the early phase of infection. The expression of Toll like receptor 3 (TLR3) was downregulated at post inoculation days (PIDs) 3, 5, and 7 in the bursas of vIBDV-infected chickens whereas TLR3 was upregulated at PIDs 3 and 5 in cIBDV-infected bursas. In vIBDV-infected bursa, TLR7 expression was downregulated at PIDs 3 and 5 and upregulated at PID 7. However, TLR7 was upregulated at PIDs 3 and 7 in cIBDV-infected bursas. The expression of MyD88 was downregulated whereas TRIF gene expression was upregulated in cIBDV- and vIBDV-infected bursa. These findings demonstrate the critical differences in bursal lesions, infiltration of T cells, expression of cytokines, chemokines and TLRs in the bursa of cIBDV-and vIBDV-infected chickens.

Interaction of infectious bursal disease virus with the immune system of poultry

“…IBDV infection in chicken promotes the expression of the pro-inflammatory cytokines and chemokines, Th1 cytokines, iNOS and MHC class I in HD11 cells in vitro (Rasoli et al, 2015) and upregulate chicken IL-12 and IL-18 in HD11 cells infected with IBDV (Khatri et al, 2005;Lee et al, 2015b). IBDV also upregulates the IL-6, IL-8 and interferons (IFNs) expression in the BF (Carballeda et al, 2014) and IL-8 (Rauf et al, 2011a). Temporary up regulation of IFN-γ, IL-2, IL-6 and down regulation of the cytokine IL-1β and type IIFNs were noted in IBDV infection (Rautenschlein et al, 2007;Eldaghayes et al, 2006).…”

“…TLR3, TLR4 and TRIF is upregulated in IBDV infection in chickens (Rauf et al, 2011a;Guo et al, 2012;Lee et al, 2015a) and chick embryo fibroblasts cells (Wong et al, 2007). In IBDV infections, expression of TLR2B, TLR4, TLR7 and MyD88 was down regulated (Rauf et al, 2011a;Guo et al, 2012) in the bursa of Fabricius (BF). Down regulation of the TLR2B indicates decreased immune responses (Guo et al, 2012).…”

“…Production of IFN-I is inhibited in IBDV infection in chickens (Eldaghayes et al, 2006) and is not induced in IBDV infected cells either in vivo or in vitro (Ye et al, 2014) although dsRNA induces IFNβ expression. IBDV infection in HD11 cells induced significantly upregulated expression levels in chicken, IFN-β (693-fold) (Lee et al, 2015b) also in BF (Rauf et al, 2011a) and IFN-γ in unvaccinated chickens (Lee et al, 2015a). IFN antiviral signal transduction pathway is controlled by the interferon regulatory factor 2 (IRF2).…”

A B-cell targeting virus disrupts potentially protective genomic methylation patterns in lymphoid tissue by increasing global 5-hydroxmethylcytosine levels

“…It is possible that IBDV downregulates Bu-1 expression in B-cells as is the case for reticuloendotheliosis virus T (V. Nair, unpublished observation), in this way, the increase in 5hmC may pertain to Bu-1 negative B-cells infected with IBDV in a mechanism that is likely to involve increased Tet 1 and 2 mRNAs ( Figure 5B). After an IBDV infection macrophages and T-cells are known to infiltrate the BF [23,36] and it is conceivable that these immune cell types are contributing to the observed increase in bursal 5hmC levels and Tet 1 and 2 mRNAs. In support of this view is the finding that both activation of macrophages and T-cells causes genomic demethylation events which may include the involvement of elevated 5hmC levels and altered Tet function [37].…”

In vitrocharacterization of chicken bone marrow-derived dendritic cells following infection with very virulent infectious bursal disease virus

“…Classical, variant and very virulent strains are capable of breaking through maternal antibody and cause lesions in the bursa. Variant strains can break maternal antibody to a greater extent than the classical strains, resulting in mortality of less than 5%; whereas classical strains induce more severe bursal lesions compared to the variant strains (Rauf et al, 2011). However, very virulent strains generally cause severe and acute pathological effects, as well as higher mortality, compared to the classical strains (Williams & Davison, 2005).…”