title: Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus.
abstract: Papillomaviruses (PV) are double stranded (ds) DNA viruses that infect epithelial cells within the skin or mucosa, most often causing benign neoplasms that spontaneously regress. The immune system plays a key role in the defense against PVs. Since these viruses infect keratinocytes, we wanted to investigate the role of the keratinocyte in initiating an immune response to canine papillomavirus-2 (CPV-2) in the dog. Keratinocytes express a variety of pattern recognition receptors (PRR) to distinguish different cutaneous pathogens and initiate an immune response. We examined the mRNA expression patterns for several recently described cytosolic nucleic acid sensing PRRs in canine monolayer keratinocyte cultures using quantitative reverse transcription-polymerase chain reaction. Unstimulated normal cells were found to express mRNA for melanoma differentiation associated gene 5 (MDA5), retinoic acid-inducible gene I (RIG-I), DNA-dependent activation of interferon regulatory factors, leucine rich repeat flightless interacting protein 1, and interferon inducible gene 16 (IFI16), as well as their adaptor molecules myeloid differentiation primary response gene 88, interferon-β promoter stimulator 1, and endoplasmic reticulum-resident transmembrane protein stimulator of interferon genes. When stimulated with synthetic dsDNA [poly(dA:dT)] or dsRNA [poly(I:C)], keratinocytes responded with increased mRNA expression levels for interleukin-6, tumor necrosis factor-α, interferon-β, RIG-I, IFI16, and MDA5. There was no detectable increase in mRNA expression, however, in keratinocytes infected with CPV-2. Furthermore, CPV-2-infected keratinocytes stimulated with poly(dA:dT) and poly(I:C) showed similar mRNA expression levels for these gene products when compared with expression levels in uninfected cells. These results suggest that although canine keratinocytes contain functional PRRs that can recognize and respond to dsDNA and dsRNA ligands, they do not appear to recognize or initiate a similar response to CPV-2.
authors.affiliation: Department of Veterinary Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. jaluff@ucdavis.edu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Luff
authors.forename: Hang
authors.initials: H
authors.lastname: Yuan
authors.forename: Maja M
authors.initials: MM
authors.lastname: Suter
authors.forename: Eliane J
authors.initials: EJ
authors.lastname: Müller
authors.forename: Richard
authors.initials: R
authors.lastname: Schlegel
authors.forename: Peter F
authors.initials: PF
authors.lastname: Moore
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D004285:Dogs; D007370:Interferon Type I / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D011067:Poly dA-dT / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051192:Receptors, Pattern Recognition / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D012333:RNA, Messenger; D051192:Receptors, Pattern Recognition; D011067:Poly dA-dT
references.citation: J Virol. 2006 Jul;80(13):6621-8
references.pmid: 16775349
references.citation: Arch Immunol Ther Exp (Warsz). 2011 Feb;59(1):41-8
references.pmid: 21234810
references.citation: PLoS One. 2011 Mar 14;6(3):e17848
references.pmid: 21423754
references.citation: FEBS J. 2009 Dec;276(24):7206-16
references.pmid: 19878308
references.citation: Vet Dermatol. 2009 Oct;20(5-6):515-32
references.pmid: 20178490
references.citation: J Clin Virol. 2005 Mar;32 Suppl 1:S7-15
references.pmid: 15753007
references.citation: Virology. 2009 Feb 20;384(2):410-4
references.pmid: 18986661
references.citation: Virology. 2007 Mar 1;359(1):28-36
references.pmid: 17034826
references.citation: J Invest Dermatol. 2007 Feb;127(2):331-41
references.pmid: 17068485
references.citation: Clin Microbiol Rev. 2012 Apr;25(2):215-22
references.pmid: 22491770
references.citation: J Virol. 2001 May;75(9):4283-96
references.pmid: 11287578
references.citation: J Clin Microbiol. 2011 Feb;49(2):707-9
references.pmid: 21159938
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Immunol. 2008 Aug 15;181(4):2694-704
references.pmid: 18684960
references.citation: Adv Dermatol. 2008;24:71-87
references.pmid: 19256306
references.citation: Biochem Biophys Res Commun. 2005 Sep 23;335(2):505-11
references.pmid: 16087162
references.citation: Clin Exp Immunol. 2007 Jan;147(1):176-83
references.pmid: 17177977
references.citation: Annu Rev Immunol. 2011;29:185-214
references.pmid: 21219183
references.citation: J Virol. 2011 Nov;85(21):11372-80
references.pmid: 21849431
references.citation: J Invest Dermatol. 2005 May;124(5):1014-25
references.pmid: 15854044
references.citation: J Invest Dermatol. 2008 Apr;128(4):932-8
references.pmid: 17928888
references.citation: Nat Rev Immunol. 2011 Feb;11(2):143-54
references.pmid: 21267015
references.citation: Virology. 2009 Feb 20;384(2):260-5
references.pmid: 19135222
references.citation: J Gen Virol. 2002 Nov;83(Pt 11):2753-2763
references.pmid: 12388811
references.citation: Vet Immunol Immunopathol. 2012 Jun 15;147(1-2):91-6
references.pmid: 22525195
references.citation: Virology. 2011 Mar 15;411(2):153-62
references.pmid: 21334037
references.citation: Vet Pathol. 1991 Mar;28(2):131-8
references.pmid: 2063514