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Synergistic effect of co-stimulation of membrane and endosomal TLRs on chicken innate immune responses

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Original languageEnglish
Pages (from-to)15-21
JournalVeterinary Immunology and Immunopathology
Early online date19 Mar 2018
Publication statusPublished - May 2018


Toll-like receptor (TLR) ligands (TLR-Ls) are critical activators of immunity and are successfully being developed as vaccine adjuvants in both mammals and birds. In this study, we investigated the synergistic effect of co-stimulation of membrane and endosomal TLRs on the innate immune responses using chicken bone marrow-derived macrophages (BMMs), and studied the effect of age on the induction of innate responses. BMMs from 1 and 4-week-old birds were stimulated with Pam3Cys-SK4 (PCSK; TLR2), synthetic monophosphoryl lipid A
(MPLA), Di[3-deoxy-D-manno-octulosonyl]-lipid A ammonium salt (KLA; TLR4),
Gardiquimod, Resiquimod (R848; TLR7), CpG class B and C (TLR21). Nitric oxide (NO) production and mRNA levels of IL-1, IL-10 and IL-12p40 showed macrophages from 4-week-old birds showed more sensitive responses compared to 1-week-old birds. The most potent TLR-Ls, PCSK, MPLA and CpG B were used to study the effect of co-stimulation on macrophages. Co-stimulation with TLR21 and TLR4 synergistically up-regulated inflammatory-related genes, as well as NO production. However, incubation of splenocytes with PCSK, MPLA and CpG B did not induce cell proliferation. Moreover, treatment with CpG
B led to significant cell death.

    Research areas

  • Chicken, Toll-like receptor, macrophage, cytokine, adjuvant

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