Toll-Like Receptor 7 Ligands Inhibit Influenza A Infection in Chickens

Stewart, Cameron R.; Bagnaud-Baule, Audrey; Karpala, Adam J.; Lowther, Sue; Mohr, Peter G.; Wise, Terry G.; Lowenthal, John W.; Bean, Andrew G. D.

doi:10.1089/jir.2011.0036

Cited by 42 publications

(32 citation statements)

References 14 publications

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“…Although 6 hour pre-treatment was not the only time to significantly limit viral replication, it was selected for further analysis because it was the time when the greatest reduction of viral titre was observed for all three ligands. These results correlate with previous studies showing that pre-treatment with TLR7 ligands 6 hours prior to infection induced potent antiviral responses [23]. This suggests that a 6 hour pre-treatment of macrophages results in the early protection of the cells against AIV, which presumably relies on the TLR-mediated activation of antiviral responses.…”

Section: Discussionsupporting

confidence: 90%

“…It has recently been demonstrated that ligands for TLR2, 4 induce Th1-like and Th2-like responses while ligands for TLR21 induce Th1-like responses in chickens [19], [21], [22]. TLR ligands are also known to induce antiviral responses, including the induction of type I IFNs in chickens [22], [23]. Considering the immunostimulatory activities of TLR ligands, these molecules have been successfully used for conferring immunity on the host against viral and bacterial pathogens [24]–[27].…”

Section: Introductionmentioning

confidence: 99%

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TLR Ligands Induce Antiviral Responses in Chicken Macrophages

et al. 2014

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Chicken macrophages express several receptors for recognition of pathogens, including Toll-like receptors (TLRs). TLRs bind to pathogen-associated molecular patterns (PAMPs) derived from bacterial or viral pathogens leading to the activation of macrophages. Macrophages play a critical role in immunity against viruses, including influenza viruses. The present study was designed to test the hypothesis that treatment of chicken macrophages with TLR ligands reduces avian influenza replication. Furthermore, we sought to study the expression of some of the key mediators involved in the TLR-mediated antiviral responses of macrophages. Chicken macrophages were treated with the TLR2, 3, 4, 7 and 21 ligands, Pam3CSK4, poly(I:C), LPS, R848 and CpG ODN, respectively, at different doses and time points pre- and post-H4N6 avian influenza virus (AIV) infection. The results revealed that pre-treatment of macrophages with Pam3CSK4, LPS and CpG ODN reduced the replication of AIV in chicken macrophages. In addition, the relative expression of genes involved in inflammatory and antiviral responses were quantified at 3, 8 and 18 hours post-treatment with the TLR2, 4 and 21 ligands. Pam3CSK4, LPS and CpG ODN increased the expression of interleukin (IL)-1β, interferon (IFN)-γ, IFN-β and interferon regulatory factor (IFR) 7. The expression of these genes correlated with the reduction of viral replication in macrophages. These results shed light on the process of immunity to AIV in chickens.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

TLR Ligands Induce Antiviral Responses in Chicken Macrophages

et al. 2014

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“…in the lung and brain in ducks, whereas the TLR7 mRNA expression in the lung and brain of the H7N1-infected chickens did not increase. According to Stewart et al (2012), the TLR7 ligand (loxoribine) can inhibit influenza A replication in vitro and in ovo. Perhaps the lack of the TLR7 response in the brain and lung of H7N1-infected chickens is related to an inadequate innate response of the host to clear the virus infection.…”

Section: Discussionmentioning

confidence: 99%

Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks

et al. 2013

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“…Recently, a study reported that loxoribine induces antiviral gene expression such as type I IFN (IFN-α and IFN-β) and IFN-γ in primary chicken splenocytes, and can inhibit influenza A replication in vitro and in ovo in a dose-dependent manner [52]. However, R848 and poly(U) cannot stimulate chicken splenocytes to upregulate the expression of type I IFN, but it can cause increased expression of IL-1β, IL-6 and IL-8 [17].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Innate sensing of viruses by pattern recognition receptors in birds

Chen

Cheng

Wang

2013

Vet Res

131

121

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Similar to mammals, several viral-sensing pattern recognition receptors (PRR) have been identified in birds including Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR). Avian TLR are slightly different from their mammalian counterparts, including the pseudogene TLR8, the absence of TLR9, and the presence of TLR1La, TLR1Lb, TLR15, and TLR21. Avian TLR3 and TLR7 are involved in RNA virus recognition, especially highly pathogenic avian influenza virus (HPAIV), while TLR15 and TLR21 are potential sensors that recognize both RNA viruses and bacteria. However, the agonist of TLR15 is still unknown. Interestingly, chickens, unlike ducks, geese and finches, lack RIG-I, however they do express melanoma differentiation-associated gene 5 (MDA5) which functionally compensates for the absence of RIG-I. Duck RIG-I is the cytosolic recognition element for HPAIV recognition, while chicken cells sense HPAIV through MDA5. However, the contributions of MDA5 and RIG-I to IFN-β induction upon HPAIV infection is different, and this may contribute to the chicken’s susceptibility to highly pathogenic influenza. It is noteworthy that the interactions between avian DNA viruses and PRR have not yet been reported. Furthermore, the role for avian Nod-like receptors (NLR) in viral immunity is largely unknown. In this review, recent advances in the field of viral recognition by different types of PRR in birds are summarized. In particular, the tissue and cellular distribution of avian PRR, the recognition and activation of PRR by viruses, and the subsequent expression of innate antiviral genes such as type I IFN and proinflammatory cytokines are discussed.

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Toll-Like Receptor 7 Ligands Inhibit Influenza A Infection in Chickens

Cited by 42 publications

References 14 publications

TLR Ligands Induce Antiviral Responses in Chicken Macrophages

TLR Ligands Induce Antiviral Responses in Chicken Macrophages

Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks

Innate sensing of viruses by pattern recognition receptors in birds

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