Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken

Bashir, Khalid; Kappala, Deepthi; Singh, Yogendra; Dar, Javeed Ahmad; Kumar, Manoj; Kumar, Ajay; Krishnaswamy, Narayanan; Dey, Sohini; Chellappa, Madhan Mohan; Goswami, T. K.; Gupta, Vivek Kumar; Ramakrishnan, Saravanan

doi:10.1038/s41598-019-44578-5

Cited by 19 publications

(9 citation statements)

References 82 publications

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“…Interestingly, we observed that some molecules of the antiviral pathway were stronger activated in the B87 group at 4 hpi, while others were not; however, the activation of macrophages and the Th1/Th2 ratio were not different between the two groups at this time point. Further, as compared to the HLJ0504-like vvIBDV group, the antiviral signaling, macrophage activation and cytokine expression in the B87 group were far more moderated during the early infection stage, consistent with the research from the earlier reports [18,19,60] in the bursa, suggesting that the activation of the antiviral response in the B87 group at 4 hpi might be transient and then downregulated which might be related to the easier dissemination of B87 and consistent with the biology of this vaccine strain.…”

Section: Discussionsupporting

confidence: 87%

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

Chen

Xiang

et al. 2022

Viruses

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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.

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Section: Discussionsupporting

confidence: 87%

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

Chen

Xiang

et al. 2022

Viruses

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“…The severity of lesions was more evident on 14th and 21st day PI. In corroboration to our findings, other researchers have also observed mild to severe changes with vacuolation and depletion of lymphoid cell in bursal follicles 27 , 30 – 32 . Immunosuppressive nature of intermediate plus vaccine due to severe lesions in BF of vaccinated chickens have also been reported by other researchers 13 , 33 .…”

Section: Discussionsupporting

confidence: 93%

Studies on immunopathological changes induced by commercial IBD live vaccines in poultry birds

Kajal,

Narang,

Jangir

et al. 2023

Sci Rep

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Intermediate plus live strain infectious bursal disease virus (IBDV) vaccines are used to control IBDV endemic infections in India. In the present study, immunopathological changes induced by commercial infectious bursal disease live vaccines with different immunization regimes were compared. A total of days old 108 Cobb broiler chicks were randomly divided into five groups with 24 chicks each in groups I, II, III and 18 chicks each in group IV and V. Group I served as control I (no immunization) and group II and III chicks were immunized with a single dose of vaccines 1 and 2 on 17th day of age (DOA), respectively. The group IV and V chicks were immunized with vaccines 1 and 2, respectively with primary dose on 17th DOA followed by booster dose on 24th DOA. Both intermediate plus live vaccines produced gross and histopathological lesions in lymphoid organs (bursa of Fabricius, thymus, spleen and caecal tonsils). Increased CD4 + , CD8 + T cells in affected bursa of Fabricius was evidenced by immunohistochemistry. Further, up-regulation in relative mRNA expression of IFN-γ, IL-1β and IL-6 were observed in bursa of Fabricius of treated birds, with maximum alteration particularly on 14th day post single immunization and 7th day post booster immunization. The findings suggest that single immunization regime on the 17th day of age showed immunization equivalent to booster immunization with lesser lesions, therefore, may be practiced and promoted in the field conditions for the better economic returns and animal welfare.

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“…Bashir et al (2019) reported the use of a combination of TLR agonists, including pam3CSK4 (TLR2 agonist) and poly I:C (TLR3 agonist), as an effective strategy to alleviate virus-induced immune suppression associated with the use of live attenuated infectious bursal disease vaccines (hot vaccines that may induce immune suppression) in chickens. This reduced immune suppression is attributed to the upregulation of IFN-β, IFN-γ, IL-12, and IL-4, and inhibition of IL-1β, IL-10, and inducible nitric oxide synthases (iNOS) expression through the synergistic effect of both TLR ligands [ 51 ]. Interestingly, in our studies, the group of embryos treated with CpG ODN 10 µg (half of the stand-alone dosage) in combination with 15 µg of poly I:C/embryo showed 100% survival in the first 7 days post-challenge ( Figure 2 b), whereas the stand-alone treatment of CpG ODN at 10 µg or poly I:C at 10 or 20 µg per embryo was not as effective as the combination.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Dosage Levels for In Ovo Administration of Innate Immune Stimulants for Prevention of Yolk Sac Infection in Chicks

Sarfraz

Nguyen

Wheler

et al. 2022

Veterinary Sciences

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Innate immune stimulants, especially toll-like receptor (TLR) ligands and agonists, are the main players in the initiation of innate immunity and have been widely studied as alternatives to antibiotics to control infection. In the present study, we characterized the dosage levels of various innate immune stimulants, including unmethylated cytosine-phosphate-guanosine dinucleotide -containing oligodeoxynucleotides (CpG ODN), polyinosinic-polycytidylic acid (poly I:C), cyclic polyphosphazene 75B (CPZ75B), avian beta-defensin 2 (ABD2), and combinations of these reagents given in ovo. Data derived from a series of animal experiments demonstrated that the in ovo administration of 10–50 µg CpG ODN/embryo (on embryonic day 18) is an effective formulation for control of yolk sac infection (YSI) due to avian pathogenic Escherichia coli (E. coli) in young chicks. Amongst the different combinations of innate immune stimulants, the in ovo administration of CpG ODN 10 µg in combination with 15 µg of poly I:C was the most effective combination, offering 100% protection from YSI. It is expected that the introduction of these reagents to management practices at the hatchery level may serve as a potential replacement for antibiotics for the reduction of early chick mortality (ECM) due to YSI/colibacillosis.

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Combination of TLR2 and TLR3 agonists derepress infectious bursal disease virus vaccine-induced immunosuppression in the chicken

Cited by 19 publications

References 82 publications

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

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

Studies on immunopathological changes induced by commercial IBD live vaccines in poultry birds

Characterization of Dosage Levels for In Ovo Administration of Innate Immune Stimulants for Prevention of Yolk Sac Infection in Chicks

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