Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes

He, Haiqi; Genovese, Kenneth J.; Swaggerty, Christina L.; MacKinnon, Kathryn M.; Kogut, Michael H.

doi:10.1016/j.dci.2011.11.006

Cited by 60 publications

(42 citation statements)

References 55 publications

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“…Significantly lower (p \ 0.05) expression levels of chicken IL-18, MHC class II, and CD86 at 16 or 24 hpi were coincident with the significant upregulation (p \ 0.05) of chicken IL-10 in chMDA5-overexpressing HD11 cells in the present study, suggesting the occurrence of immune regulation. Chicken monocytes stimulated with poly(I:C) and CpG-ODN have been reported to upregulate chicken IL-10, indicating the existence of a mechanism to control excessive inflammation [13]. Therefore, chMDA5 overexpression in HD11 cells in the present study may induce a strong and long-term type I IFN response, resulting in the upregulation of antiviral genes and proinflammatory cytokines and activation of chicken IL-10 to prevent excessive inflammation.…”

Section: Discussionmentioning

confidence: 90%

Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages

Lee

Lin

2015

Arch Virol

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The objective of the present study was to determine if chicken melanoma-differentiation-associated gene 5 (MDA5) senses infectious bursal disease virus infection to induce innate immunity that bridges to adaptive immunity. During IBDV infection in HD11 cells, IBDV titers and RNA loads increased up to 3.4 × 10(7) plaque-forming units (PFU)/mL and 1114 ng/µL, respectively, at 24 hours postinfection (hpi). IBDV infection in HD11 cells induced significantly upregulated (p < 0.05) expression levels of chicken MDA5 (59-fold), interferon-β (IFN-β) (693-fold), dsRNA-dependent protein kinase (PKR) (4-fold), 2', 5'-oligoadenylate synthetase (OAS) (286-fold), myxovirus resistance gene (Mx) (22-fold), interleukin-1β (IL-1β) (5-fold), IL-6 (146-fold), IL-8 (4-fold), IL-10 (4-fold), inducible nitric oxide synthase (iNOS) (15-fold), and major histocompatibility complex class I (MHC class I) (4-fold). Nitric oxide production in the culture supernatants increased significantly (p < 0.05) up to 6.5 μM at 24 hpi. The expressed chMDA5 and IBDV-derived dsRNA were localized in the cytoplasm of HD11 cells during IBDV infection. ChMDA5-knockdown HD11 cells had significantly higher (p < 0.05) IBDV RNA loads at 24 hpi and significantly lower (p < 0.05) nitric oxide production and expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-18, IL-10, iNOS, MHC class I and CD86 at 24 hpi. In addition, chMDA5 overexpression in HD11 cells resulted in significantly reduced (p < 0.05) IBDV titers and RNA loads and significantly increased (p < 0.05) nitric oxide production at 16 and 24 hpi. It also resulted in significantly higher (p < 0.05) expression levels of chicken MDA5, IFN-β, PKR, OAS, Mx, IL-1β, IL-6, IL-8, IL-12(p40), IL-10 and iNOS at 2 hpi. In conclusion, the results indicate that chMDA5 senses IBDV infection in chicken macrophages, and this is associated with IBDV-induced expression of IFN-β and initiation of an innate immune response that in turn activates the adaptive immune response and limits IBDV replication.

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Section: Discussionmentioning

confidence: 90%

Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages

Lee

Lin

2015

Arch Virol

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“…In the present study, an upregulated TLR21 expression was observed in chickens on BMDand YDM-supplemented diets in the cecal tonsil and bursa of Fabricius, whereas expression in the spleen was downregulated in the YDM treatment. Chicken TLR21 is a functional homolog to mammalian TLR9 and recognizes CpG oligodeoxynucleotides (CpG-ODN; He et al, 2012). Various studies have reported the immune stimulatory characteristics of CpG-ODN in chicken (Patel et al, 2008;Brownlie et al, 2009;He et al, 2011b).…”

Section: Discussionmentioning

confidence: 99%

Performance, histomorphology, and Toll-like receptor, chemokine, and cytokine profile locally and systemically in broiler chickens fed diets supplemented with yeast-derived macromolecules

et al. 2013

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The turnover of intestinal epithelial cells is a dynamic process that includes adequate cell proliferation and maturation in the presence of microbiota and migration and seeding of immune cells in early gut development in chickens. We studied the effect of yeastderived macromolecules (YDM) on performance, gut health, and immune system gene expression in the intestine of broiler chickens. One thousand eighty 1-d-old birds, with 60 birds per pen and 6 pens per treatment, were randomly assigned to 3 treatment diets; a diet containing monensin (control), control diet supplemented with bacitracin methylene disalycylate (BMD), and BMD diet supplemented with YDM. Feed intake, BW, mortality, ileum histomorphology, and gene expression of Toll-like receptors (TLR2b, TLR4, and TLR21), cytokines [interferon (IFN)-γ, IFN-β, , and transforming growth factor (TGF)-β4], and cluster of differentiation (CD)40 in the ileum, cecal tonsil, bursa of Fabricius, and spleen were assessed. No significant overall difference in performance in terms of feed intake, BW gain, and G:F was observed among treatments (P > 0.05). The YDM diet resulted in significantly higher villi height and villi height:crypt depth ratio compared with BMD and control diets (P < 0.05). A significantly lower mortality was observed in the YDM treatment compared with both control and BMD treatments. Compared with the control, gene expression analysis in YDM treatment showed no major change in response in the ileum, whereas higher CD40, in the cecal tonsil; TLR2b, TLR4, TLR21, and TGF-β4 in the bursa of Fabricius; and TLR4, IL12p35, in the spleen was observed (P < 0.05). In conclusion, supplementation of YDM supports pro-and anti-inflammatory cytokine production via T helper type 1 and 2 (Th1 and Th2) cell-associated pathways both locally and systemically with a stronger additive effect in the cecal tonsil in the presence of BMD in the diet of chickens.

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“…CpG and poly I:C activate distinct TLRs, and the combination of the two ligands results in synergistic immune effects [16][17][18]. Table 1 shows the unique peptide phosphorylation events that occurred when cells were stimulated with both CpG and poly I:C. These unique events strongly indicated that novel cellular activities were induced by the combination of the two ligands.…”

Section: H Stimulation 4 H Stimulation Cpgmentioning

confidence: 99%

“…Interaction between TLR3 and TLR21 agonists poly I:C and CpG has been reported to synergize in the expression of proinflammatory cytokines and chemokines and the production of NO in chicken monocytes [16,17]. The synergistic interaction between the TLR3 and TLR21 pathways also produces a stronger Th1-biased immune response in chicken monocytes [18].…”

Section: Introductionmentioning

confidence: 98%

Combined CpG and poly I:C stimulation of monocytes results in unique signaling activation not observed with the individual ligands

Arsenault

Kogut

2013

Cellular Signalling

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Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes

Cited by 60 publications

References 55 publications

Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages

Role of chicken melanoma differentiation-associated gene 5 in induction and activation of innate and adaptive immune responses to infectious bursal disease virus in cultured macrophages

Performance, histomorphology, and Toll-like receptor, chemokine, and cytokine profile locally and systemically in broiler chickens fed diets supplemented with yeast-derived macromolecules

Combined CpG and poly I:C stimulation of monocytes results in unique signaling activation not observed with the individual ligands

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