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A Toll-like receptor 3 agonist (polyI:C) elicits innate host responses in the spleen and lungs of chickens.

ABSTRACT: Double-stranded (ds) RNA interacts with host Toll-like receptor (TLR-3), leading to the induction of anti-viral host responses. The present study was designed to compare different routes of administration of a synthetic dsRNA (polyI:C) for induction of innate responses in chicken spleen and lungs. Chickens were treated with polyI:C via the aerosol, intra-air sac (i.a.s.), and intramuscular (IM) routes. Spleen and lungs were collected at 0, 2, 6, 12, and 24 h post-treatment and the expression of innate defence genes was quantified by real-time reverse transcriptase polymerase chain reaction (RT-PCR). There was an up-regulation of interferon (IFN)-?, TLR-3, and Toll/interleukin 1 receptor domain-containing adaptor protein inducing IFN-? (TRIF) at 6 h post-treatment in the spleen via IM administration of polyI:C. There was also an increase in the expression of TLR-3 and TRIF in the spleen at 2 h post-treatment via the i.a.s. route. The expression of IFN-? and TRIF was upregulated at 6 h post-treatment via the i.a.s. route in the lungs. Overall, our results indicate that administration of polyI:C can locally and systemically induce the expression of innate response genes depending on the route.

SUBMITTER: Parvizi P

PROVIDER: S-EPMC3384288 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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A Toll-like receptor 3 agonist (polyI:C) elicits innate host responses in the spleen and lungs of chickens.

Parvizi Payvand P Mallick Amirul Islam AI Haq Kamran K Schlegel Benjamin B Sharif Shayan S

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 20120701 3

Double-stranded (ds) RNA interacts with host Toll-like receptor (TLR-3), leading to the induction of anti-viral host responses. The present study was designed to compare different routes of administration of a synthetic dsRNA (polyI:C) for induction of innate responses in chicken spleen and lungs. Chickens were treated with polyI:C via the aerosol, intra-air sac (i.a.s.), and intramuscular (IM) routes. Spleen and lungs were collected at 0, 2, 6, 12, and 24 h post-treatment and the expression of ...[more]

PMID: 23277704

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Project description:BackgroundNewborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization.ObjectiveSmall-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs.MethodsChemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo, and a range of TLR8 agonist-encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow-derived DCs enabled benchmarking of the TLR8 agonist-encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25-loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice.ResultsAlthough alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited TH-polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist-adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4+ T-cell numbers.ConclusionTLR8 agonist-encapsulating polymersomes hold substantial potential for early-life immunization against intracellular pathogens. Overall, our study represents a novel approach for rational design of early-life vaccines.

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A Toll-like receptor 3 agonist (polyI:C) elicits innate host responses in the spleen and lungs of chickens.

Publications

A Toll-like receptor 3 agonist (polyI:C) elicits innate host responses in the spleen and lungs of chickens.

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