Differential Modulation of Innate Antiviral Profiles in the Intestinal Lamina Propria Cells of Chickens Infected with Infectious Bursal Disease Viruses of Different Virulence

Abstract

Infectious bursal disease virus (IBDV) is one of the most important infectious diseases of poultry around the world. Gut-associated lymphoid tissues (GALT) are the first line of defense of the host against the infection. The purpose of this study was to investigate the role of innate immune antiviral signaling triggered by Toll-like receptor 3 (TLR3), as well as macrophage activation and cytokine response in the intestinal lamina propria (ILP) cells after the oral challenge of IBDV in relation to IBDV virulence and disease pathogenesis. The results showed that the expression levels of TLR3, IRF7, IFN-α/β and the corresponding downstream antiviral factors OAS, PKR and Mx were all upregulated in the SPF chicken ILP cells at 8 h post-infection (hpi) and 12 hpi. Similarly, macrophages were activated, with the initial macrophage M1 activation observed at 8 hpi, but then it rapidly shifted to a non-protective M2-type. Both Th1 (IFN-γ, TNF-α, IL-12) and Th2 (IL-4 and IL-10) types of cytokines were differentially upregulated during the early stage of infection; however, the Th1 cytokines exhibited stronger activation before 8 hpi compared to those of the Th2 cytokines. Interestingly, differential regulations of gene expression induced by different IBDV strains with different virulence were detected. The HLJ0504-like very virulent (vv) IBDV strain NN1172 induced stronger activation of TLR3-IFN-α/β pathway, macrophages and the Th1/2 cytokines’ expression, compared to those induced by the attenuated strain B87 at 8 hpi and 12 hpi in the ILP cells. In conclusion, the innate antiviral response mediated by the TLR3-IRF7 pathway, macrophage activation and cytokine expression in the GALT cells at the early stage of IBDV infection was differentially modulated, and the HLJ0504-like vvIBDV strain triggered stronger activation than the attenuated vaccine strain, and that may play an important role in the progression of disease.

RNA-seq reveals role of cell-cycle regulating genes in the pathogenicity of a field very virulent infectious bursal disease virus

“…In Nakanishi et al 's review (71), IL-18 normally can enhance the IL-12-driven Th1 immune responses after stimulation, however, it can also stimulate Th2 immune responses in the absence of IL-12; further, overproduction of IL-18 is responsible for tissue injury. Considering the histological changes observed in the thymus, it is conceivable that a predominant Th2 cell response may be underway during this stage of infection, potentially exacerbating disease progression, which consistent with our previous research, where we reported that Th2 cell response plays important role in the IBD progression (72). In this study, we also detected cytokines, chemokines at the mRNA level as evidenced by up-regulation genes enriched in the cytokine-cytokine receptor interaction pathway which is consistent with many researches (15,16).…”

Expression of Toll‐like receptors and host defence peptides in the cecum of chicken challenged with Eimeria tenella

“…Similar to the chTLRs above‐mentioned, chTLR3, chTLR5 and chTLR15 were upregulated after chickens were infected with E. tenella . chTLR3 stimulates immune system responses by recognising double‐stranded RNA of viruses, and expression level of chTLR3 was higher in the early stages of infection, and correlated with virulence and viral load during IBDV infection 46 . In the present study, chTLR3 expression was highest at 72 h post‐infection with E. tenella , consistent with IBDV infection.…”

“…chTLR3 stimulates immune system responses by recognising double-stranded RNA of viruses, and expression level of chTLR3 was higher in the early stages of infection, and correlated with virulence and viral load during IBDV infection. 46 In the present study, chTLR3…”

Analysis of the global origin, evolution and transmission dynamics of the emerging novel variant IBDV (A2dB1b): The accumulation of critical aa‐residue mutations and commercial trade contributes to the emergence and transmission of novel variants

“…Infectious bursal disease (IBD) is an acute, highly contagious viral infection of young chickens that has lymphoid tissue, especially the bursa of Fabricius as its primary target (Berg, 2000). IBDV infection has the ability to lyse B lymphocytes and destroy the follicular centres of bursa, leading to severe immunosuppression due to a failure to replenish B cells in a timely manner (Chen et al., 2022; Wang, Huang, Zhang, et al., 2021). Two serotypes of IBDVs have been recognized: serotype 1 (pathogenic) and serotype 2 (nonpathogenic) (Ismail et al., 1988; Jackwood et al., 1982).…”