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Clinical and Vaccine Immunology, June 2009, p. 866-878, Vol. 16, No. 6
1071-412X/09/$08.00+0     doi:10.1128/CVI.00035-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Accessory-Cell-Mediated Activation of Porcine NK Cells by Toll-Like Receptor 7 (TLR7) and TLR8 Agonists {triangledown} ,{dagger}

Felix N. Toka,1,2 Charles K. Nfon,1 Harry Dawson,3 and William T. Golde1*

Plum Island Animal Disease Center, ARS, USDA, P.O. Box 848, Greenport, New York 11944,1 Warsaw University of Life Sciences, Faculty of Veterinary Medicine, Department of Preclinical Sciences, Warsaw, Poland,2 Beltsville Area Research Center, ARS, USDA, Beltsville, Maryland 207053

Received 23 January 2009/ Returned for modification 20 February 2009/ Accepted 24 March 2009

The induction of innate immune responses by toll-like receptor (TLR) agonists is the subject of intense investigation. In large part, this reflects the potential of such compounds to be effective vaccine adjuvants. For that reason, we analyzed the activation of innate cells in swine by TLR7 and TLR8 agonists. These agonists activated porcine NK cells by increasing gamma interferon (IFN-{gamma}) expression and perforin storage. The activation of porcine NK cells was mediated by accessory cells, since their depletion resulted in reduced cytotoxicity toward target cells. Accessory cells were stimulated to produce interleukin 12 (IL-12), IL-15, IL-18, and IFN-{alpha} after treatment with TLR7 or TLR8 agonists. Neutralization of these cytokines reduced but did not completely inhibit the induction of NK cell cytotoxicity. Direct stimulation of NK cells with TLR7 or TLR8 agonists resulted in minimal cytotoxicity but levels of IFN-{gamma} equivalent to those detected in the presence of accessory cells. Porcine NK cells express both TLR7 and TLR8 mRNAs, and treatment with these TLR agonists induced higher mRNA expression levels of TRAIL and IL-15R{alpha}, which may contribute to the activity of NK cells. These data indicate that TLR7 and TLR8 agonists indirectly or directly activate porcine NK cells but that optimum levels of activation require cytokine secretion by accessory cells activated by these compounds. Interestingly, NK cells activated by TLR7 or TLR8 agonists were cytotoxic against foot-and-mouth disease virus (FMDV)-infected cells in vitro, indicating that these TLR agonists may be beneficial as adjuvants to stimulate the innate immunity against FMDV.

* Corresponding author. Mailing address: Plum Island Animal Disease Center, ARS, USDA, P.O. Box 848, Greenport, NY 11944. Phone: (631) 323-3249. Fax: (631) 323-3006. E-mail: william.golde{at}ars.usda.gov

{triangledown} Published ahead of print on 15 April 2009.

{dagger} Supplemental material for this article may be found at http://cvi.asm.org/.

Clinical and Vaccine Immunology, June 2009, p. 866-878, Vol. 16, No. 6
1071-412X/09/$08.00+0     doi:10.1128/CVI.00035-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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