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Flagellin A Toll-Like Receptor 5 Agonist as an Adjuvant in Chicken Vaccines

Shishir Kumar Gupta, Preety Bajwa, Rajib Deb, Madhan Mohan Chellappa, Sohini Dey
T. S. Alexander, Editor
Shishir Kumar Gupta
aRecombinant DNA Lab, Indian Veterinary Research Institute, Izatnagar, Bareilly (UP), India
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Preety Bajwa
bGBPUAT, Pantnagar, Uttarakhand, India
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Rajib Deb
aRecombinant DNA Lab, Indian Veterinary Research Institute, Izatnagar, Bareilly (UP), India
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Madhan Mohan Chellappa
aRecombinant DNA Lab, Indian Veterinary Research Institute, Izatnagar, Bareilly (UP), India
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Sohini Dey
aRecombinant DNA Lab, Indian Veterinary Research Institute, Izatnagar, Bareilly (UP), India
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T. S. Alexander
Roles: Editor
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DOI: 10.1128/CVI.00669-13
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    FIG 1

    TLR5 signaling. Flagellin binding to TLR recruits adaptor protein MyD88, leading to the activation of IRAK-1/4 and TRAF-6 and resulting in the activation of NF-κB, which induces the expression of proinflammatory cytokines.

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    FIG 2

    Mechanism of induction of the type of immune responses following TLR activation.

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    FIG 3

    TLR ligands affect many immunological processes to elicit an elevated immune response.

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    FIG 4

    Structure of flagellin with four major domains indicated (NCBI; GenBank accession no. KF589316).

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  • TABLE 1

    Summary of TLR5-mediated adjuvant action of flagellated Salmonella strains

    Study modelResult(s)Reference
    Chicken kidney cells (CKC)Flagellated strains S. Enteritidis and S. Gallinarum (Fla+) induced higher levels of CXCLi2, iNOS, and IL-6; less mortality with flagellated strains73
    Chicken (in vivo)Flagellin-deficient mutants exhibited enhanced ability for systemic infections; lower levels of IL-1β and CXCLi2 than wild type75
    Chicken PBMCsTLR5-flagellin-mediated upregulation of IL-1β, IL-6, CXCLi2, and CCLi2 expression in S. Enteritidis-infected cells74
    CKC and HD11Flagellated S. Enteritidis and S. Typhimurium induced more IL-6, CXCLi1, CXCLi2, and iNOS than nonflagellated S. Pullorum and S. Gallinarum105
    HeLa cells expressing chicken TLR5Induced more NF-κB in response to S. Enteritidis infection in a dose- and flagellin-dependent manner72
    Chicken (in vivo)Reduced levels of IL-1β and IL-6 and enhanced ability to establish systemic infection after challenge with aflagellar S. Typhimurium23
    Intestinal epithelial cellsFlagellin-deficient S. Typhimurium mutant (fliC, fljB, and flhD) failed to elicit IL-8 expression52
  • TABLE 2

    Flagellin as an adjuvant in chicken: applications in vitro

    Cell categoryResponse(s)Reference
    Chicken PBMCsUpregulation of both IL-12 and IL-4 as well as IL-679
    Chicken splenocytesInduction of a mixed Th1- and Th2-like response80
    Chicken heterophilsUpregulation of IL-6 and CXCLi2100
    HeLa cells with chicken TLR5Upregulation of TLR5-flagellin-mediated NF-κB expression72
    Chicken monocytesInduction of nitric oxide production78
    Chicken heterophilsIncreased oxidative burst; significant production of proinflammatory cytokines and chemokines77
    CEF, CKC HD11 cellsSignificant upregulation of IL-1β23
    Chicken heterophilsSignificant upregulation of IL-1β, IL-6, and IL-8 and increased oxidative burst76
  • TABLE 3

    Flagellin as an adjuvant in chicken: applications in vivo

    AntigenResult(s)Reference
    Immune-mapped protein-1 (IMP-1) of Eimeria tenella (EtIMP1)Flagellin-fused EtIMP1 elicited a stronger protective immune response; reduced mortality83
    Avian influenza virusIncreased IgY and IgA82
    Salmonella enterica serovar EnteritidisIncreased IgA and decreased bacterial counts34
    Campylobacter jejuniIncreased Ig and decreased bacterial load35
    Salmonella enterica serovar EnteritidisReduced mortality81
    Campylobacter jejuniIncreased Ig and decreased bacterial load101
  • TABLE 4

    Adjuvant effect of combinations of TLR agonists on chicken immune cells

    TLR combinationCell categoryResult(s)Reference
    TLR5 and TLR4Chicken PBMCsSynergistic upregulation of NO, IL-6, and IL-12; antagonistic downregulation of IL-479
    TLR3 and TLR21Chicken RBCsaSynergistic upregulation of type 1 IFNs102
    TLR3 and TLR21Chicken monocytesSynergistic upregulation of IFN-γ and IL-10103
    TLR4 and TLR21Chicken thrombocytesSynergistic upregulation of IL-1β, IL-6, and IL-8104
    TLR3 and TLR21Chicken monocytesSynergistic upregulation of NO, IL-1β, IL-6, and MIP-1β92
    TLR3 and TLR21Chicken monocytesSynergistic upregulation of NO production94
    • ↵a RBCs, red blood cells.

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Flagellin A Toll-Like Receptor 5 Agonist as an Adjuvant in Chicken Vaccines
Shishir Kumar Gupta, Preety Bajwa, Rajib Deb, Madhan Mohan Chellappa, Sohini Dey
Clinical and Vaccine Immunology Feb 2014, 21 (3) 261-270; DOI: 10.1128/CVI.00669-13

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Flagellin A Toll-Like Receptor 5 Agonist as an Adjuvant in Chicken Vaccines
Shishir Kumar Gupta, Preety Bajwa, Rajib Deb, Madhan Mohan Chellappa, Sohini Dey
Clinical and Vaccine Immunology Feb 2014, 21 (3) 261-270; DOI: 10.1128/CVI.00669-13
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  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • TLR5 SIGNALING
    • TLR SIGNALING AFFECTS MANY IMMUNOLOGICAL PROCESSES TO ENHANCE THE IMMUNE RESPONSE
    • FLAGELLIN: A TLR5 AGONIST
    • CONCLUSION
    • ACKNOWLEDGMENT
    • REFERENCES
    • Author Bios
  • Figures & Data
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