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United States Department of Agriculture

Agricultural Research Service

Research Project: GENETIC AND BIOLOGICAL DETERMINANTS OF AVIAN TUMOR VIRUS PATHOGENICITY, TRANSMISSION, AND EVOLUTION

Location: Avian Disease and Oncology Laboratory

Title: The effects of administration of ligands for Toll-like receptor 4 and 21 against Marek’s disease in chickens

Authors
item Parvizi, Payvand -
item Abdul-Careem, Mohamed -
item Mallick, Amirul -
item Haq, Kamran -
item Haghighi, Hamid -
item Orouji, Shahriar -
item Heidari, Mohammad
item Behboudi, Shahriar -
item Sharif, Shayan -

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 30, 2014
Publication Date: February 13, 2014
Citation: Parvizi, P., Abdul-Careem, M.F., Mallick, A.I., Haq, K., Haghighi, H.R., Orouji, S., Heidari, M., Behboudi, S., Sharif, S. 2014. The effects of administration of ligands for Toll-like receptor 4 and 21 against Marek’s disease in chickens. Vaccine. 32(17):1932-1938. Available: http://dx.doi.org/10.1016/j.vaccine.2014.01.082.

Interpretive Summary: Toll-like receptors (TLRs) are pattern recognition receptors expressed on the surfaces of certain cells that recognize conserved pathogen-associated molecular patterns and trigger pro-inflammatory cytokine production such as interleukins and interferons. Among the innate defense mechanisms, TLRs play an important role in recognition of pathogens and elicitation of innate and adaptive immune responses against viruses and bacteria. In this study, we examined the effects of various TLR ligands on the development of Marek’s disease in chickens. Specific-pathogen free chickens were treated with a series of TLR ligands that interact with TLR3, TLR9 and TLR21. Chickens were treated with lipopolysaccharide (LPS; Endotoxin of Gram negative bacteria) as a TLR4 agonist and specific short single-stranded synthetic DNA molecules (CpG oligodeoxynucleotides) as TLR21 agonist before being challenged with the RB1B strain of Marek’s disease virus (MDV) via the respiratory route. The results demonstrated that the administration of LPS or above-mentioned short DNA molecules, but not phosphate buffered saline, delayed disease onset and reduced MDV genome copy number in the spleens of infected chickens. Our data demonstrate that TLR4 and TLR21 agonists modulate anti-virus innate immunity including cytokine responses in MD-infected chicken and this response can only delay, but not inhibit, disease progression.

Technical Abstract: Ligands for Toll-like receptors (TLRs) are known to stimulate immune responses, leading to protection against bacterial and viral pathogens. Here, we aimed to examine the effects of various TLR ligands on the development of Marek’s disease in chickens. Specific-pathogen free chickens were treated with a series of TLR ligands that interact with TLR3, TLR9 and TLR21. In a pilot study, it was determined that TLR4 and TLR21 ligands are efficacious, in that they could reduce the incidence of Marek’s disease tumors in infected birds. Hence, in a subsequent study, chickens were treated with lipopolysaccharide (LPS) as a TLR4 and CpG oligodeoxynucleotides (ODN) as TLR21 agonists before being challenged with the RB1B strain of Marek’s disease virus (MDV) via the respiratory route. The results demonstrated that the administration of LPS or CpG ODN, but not PBS or non-CpG ODN, delayed disease onset and reduced MDV genome copy number in the spleens of infected chickens. Taken together, our data demonstrate that TLR4 and 21 agonists modulate anti-virus innate immunity including cytokine responses in MD-infected chicken and this response can only delay, but not inhibit, disease progression.

Last Modified: 10/23/2014
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