Chundi Tian , Zhihao Ren , Shang Chang , Wenping Cui , Peng Zhao , Yixin Wang
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引用次数: 0
Abstract
Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by infectious bursal disease virus (IBDV). Immune checkpoint molecules are vital for regulating immune equilibrium, preventing autoimmune responses, and controlling the scale and duration of immune reactions. These molecules are implicated in the immunosuppressive mechanisms initiated by viral infections. Currently, the correlation between IBDV infection and the expression of immune checkpoint molecules is not clearly defined. In this study, White Leghorn SPF chickens were inoculated with very virulent (vvIBDV), attenuated (attIBDV), or novel variant (nvIBDV) IBDV strains. Using real-time PCR, we quantified immune checkpoint genes and cytokines in the bursa of fabricius (BF), thymus, spleen, and peripheral blood mononuclear cells (PBMCs). The findings revealed a significant upregulation of immune checkpoint genes (PD-1, PD-L1, PD-L2, LAG3, CTLA4) in the BF, thymus, spleen, and PBMCs following infection with various virulent strains of IBDV compared to control tissues. Specifically, PD-L1 in BF surged to 7.32-fold (vvIBDV, 3 dpi), 7.44-fold (attIBDV, 3 dpi), and 6.47-fold (nvIBDV, 3 dpi) compared to controls. PD-L2 in spleen surged to 7.66-fold (attIBDV, 21 dpi), and 7.82-fold (nvIBDV, 21 dpi) compared to controls. Moreover, the expression levels of inhibitory and pro-inflammatory cytokines (TGF-β2, IL-10, IL-6, IL-1β, TNF-α) were notably elevated in infected tissues compared to control tissues, with IL-1β upregulated by 7.47-fold in BF at 3 dpi. TGF-β2 in spleen surged to 8.16-fold (vvIBDV, 21 dpi), 6.33-fold (attIBDV, 21 dpi), and 7.61-fold (nvIBDV, 21 dpi). These results suggest that IBDV infection in SPF chickens induces robust upregulation of immune checkpoint molecules (PD-1, PD-L1, PD-L2, LAG3, CTLA4) and cytokines (TGF-β2, IL-10, IL-6, IL-1β, TNF-α), correlating with viral virulence and immunosuppression. Our findings suggest that immune checkpoint dysregulation may contribute to IBDV pathogenesis, particularly in mediating sustained immunosuppression in poultry.
期刊介绍:
The journal reports basic, comparative and clinical immunology as they pertain to the animal species designated here: livestock, poultry, and fish species that are major food animals and companion animals such as cats, dogs, horses and camels, and wildlife species that act as reservoirs for food, companion or human infectious diseases, or as models for human disease.
Rodent models of infectious diseases that are of importance in the animal species indicated above,when the disease requires a level of containment that is not readily available for larger animal experimentation (ABSL3), will be considered. Papers on rabbits, lizards, guinea pigs, badgers, armadillos, elephants, antelope, and buffalo will be reviewed if the research advances our fundamental understanding of immunology, or if they act as a reservoir of infectious disease for the primary animal species designated above, or for humans. Manuscripts employing other species will be reviewed if justified as fitting into the categories above.
The following topics are appropriate: biology of cells and mechanisms of the immune system, immunochemistry, immunodeficiencies, immunodiagnosis, immunogenetics, immunopathology, immunology of infectious disease and tumors, immunoprophylaxis including vaccine development and delivery, immunological aspects of pregnancy including passive immunity, autoimmuity, neuroimmunology, and transplanatation immunology. Manuscripts that describe new genes and development of tools such as monoclonal antibodies are also of interest when part of a larger biological study. Studies employing extracts or constituents (plant extracts, feed additives or microbiome) must be sufficiently defined to be reproduced in other laboratories and also provide evidence for possible mechanisms and not simply show an effect on the immune system.