In vivo administration of ligands for chicken toll-like receptors 4 and 21 induces the expression of immune system genes in the spleen

Paul, Michael St.; Mallick, Amirul Islam; Haq, Kamran; Orouji, Shahriar; Abdul-Careem, Mohamed Faizal; Sharif, Shayan

doi:10.1016/j.vetimm.2011.09.004

Cited by 65 publications

(22 citation statements)

References 62 publications

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“…In support of this notion, we found that thrombocytes express transcripts for type I interferons (IFN-α and β), as well as the interferon inducible gene 2′–5′ OAS, which all are involved in anti-viral responses, including responses against AIV [23], [24] . Furthermore, we found that thrombocytes up-regulate IFN-α in response to treatment with LPS, which is similar to what we observed in vivo in the spleens of chickens treated with LPS [21]. Interestingly, in the present experiment we observed a significant up-regulation of IFN-α in response to CpG ODN.…”

Section: Discussionsupporting

confidence: 91%

“…There was an up-regulation of IL-12 in thrombocytes response to LPS and CpG ODN, which raises the possibility that thrombocytes may be one of the cell subsets that contribute to the T H 1-like responses observed in vivo following administration of LPS and CpG [21]. Interestingly, it has recently been proposed that highly pathogenic avian influenza virus (AIV) has the potential to replicate inside chicken thrombocytes and promote the up-regulation of some interferon inducible genes [15], which may suggest thrombocytes as one of the cell subsets contributing to the pro-inflammatory response observed following AIV infection [22].…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Chicken Thrombocyte Responses to Toll-Like Receptor Ligands

et al. 2012

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Thrombocytes are the avian equivalent to mammalian platelets. In addition to their hemostatic effects, mammalian platelets rely in part on pattern recognition receptors, such as the Toll-like receptors (TLR), to detect the presence of pathogens and signal the release of certain cytokines. Ligands for TLRs include lipopolysaccharide (LPS), which is bound by TLR4, as well as unmethylated CpG DNA motifs, which are bound by TLR9 in mammals and TLR21 in chickens. Similar to mammalian platelets, avian thrombocytes have been shown to express TLR4 and secrete some pro-inflammatory cytokines in response to LPS treatment. However, the full extent of the contributions made by thrombocytes to host immunity has yet to be elucidated. Importantly, the mechanisms by which TLR stimulation may modulate thrombocyte effector functions have not been well characterized. As such, the objective of the present study was to gain further insight into the immunological role of thrombocytes by analyzing their responses to treatment with ligands for TLR4 and TLR21. To this end, we quantified the relative expression of several immune system genes at 1, 3, 8 and 18 hours post-treatment using real-time RT-PCR. Furthermore, production of nitric oxide and phagocytic activity of thrombocytes was measured after their activation with TLR ligands. We found that thrombocytes constitutively express transcripts for both pro- and anti-inflammatory cytokines, in addition to those associated with anti-viral responses and antigen presentation. Moreover, we found that both LPS and CpG oligodeoxynucleotides (ODN) induced robust pro-inflammatory responses in thrombocytes, as characterized by more than 100 fold increase in interleukin (IL)-1β, IL-6 and IL-8 transcripts, while only LPS enhanced nitric oxide production and phagocytic capabilities. Future studies may be aimed at examining the responses of thrombocytes to other TLR ligands.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Characterization of Chicken Thrombocyte Responses to Toll-Like Receptor Ligands

et al. 2012

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“…Real-time PCR was performed using SYBR green dye in a LightCycler 480 II to quantify the MDV genome copy numbers and cytokine gene expression (Roche Diagnostics, Laval, Quebec) as described previously 50 , 51 . Primer sequences of target and reference genes are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

The effects of in ovo administration of encapsulated Toll-like receptor 21 ligand as an adjuvant with Marek’s disease vaccine

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et al. 2018

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Marek’s Disease Virus (MDV) is the causative agent of a lymphoproliferative disease, Marek’s disease (MD) in chickens. MD is only controlled by mass vaccination; however, immunity induced by MD vaccines is unable to prevent MDV replication and transmission. The herpesvirus of turkey (HVT) vaccine is one of the most widely used MD vaccines in poultry industry. Vaccines can be adjuvanted with Toll-like receptor ligands (TLR-Ls) to enhance their efficacy. In this study, we examined whether combining TLR-Ls with HVT can boost host immunity against MD and improve its efficacy. Results demonstrated that HVT alone or HVT combined with encapsulated CpG-ODN partially protected chickens from tumor incidence and reduced virus replication compared to the control group. However, encapsulated CpG-ODN only moderately, but not significantly, improved HVT efficacy and reduced tumor incidence from 53% to 33%. Further investigation of cytokine gene profiles in spleen and bursa of Fabricius revealed an inverse association between interleukin (IL)-10 and IL-18 expression and protection conferred by different treatments. In addition, the results of this study raise the possibility that interferon (IFN)-β and IFN-γ induced by the treatments may exert anti-viral responses against MDV replication in the bursa of Fabricius at early stage of MDV infection in chickens.

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“…Quantitative real-time PCR was performed on diluted cDNA (1∶10 in DEPC treated water) using SYBR green dye in a LightCycler 480 II (Roche Diagnostics GmbH, Mannheim, DE) as previously described [21], [41]. Briefly, the amplification conditions consisted of pre-incubation for 10 min at 94°C, followed by 45 cycles of 95°C for 10 s, 55–64°C annealing as described in table 2 for each of the primers for 5 s and elongation and signal acquisition (single mode) at 72°C for 10 s. Melting curve analysis was done in three steps; 95°C for 10 s, cooling to 65°C for 1 min and heating to 97°C.…”

Section: Methodsmentioning

confidence: 99%

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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In vivo administration of ligands for chicken toll-like receptors 4 and 21 induces the expression of immune system genes in the spleen

Cited by 65 publications

References 62 publications

Characterization of Chicken Thrombocyte Responses to Toll-Like Receptor Ligands

Characterization of Chicken Thrombocyte Responses to Toll-Like Receptor Ligands

The effects of in ovo administration of encapsulated Toll-like receptor 21 ligand as an adjuvant with Marek’s disease vaccine

TLR Ligands Induce Antiviral Responses in Chicken Macrophages

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