[en] Idiopathic lymphoplasmacytic rhinitis (LPR) and sino-nasal aspergillosis (SNA) are among the most common causes of nasal discharge in dogs. The pathogenesis of both diseases is poorly understood. Some have proposed that LPR is a chronic inflammatory response to an inhaled irritant, pollutant or allergen, but others suggest that most cases of LPR constitute undiagnosed cases of SNA. Local immune dysfunction is thought to permit opportunist infection in canine SNA. This study investigates the nature of the local tissue immune response mounted in canine LPR and SNA in order to determine whether these diseases have similar or distinct pathogenesis. Quantitative reverse transcriptase polymerase chain reaction was carried out on RNA isolated from nasal biopsies from diseased and control dogs, using specific assays designed to amplify messenger RNA (mRNA), encoding a panel of cytokines and chemokines. SNA was associated with significantly increased expression of mRNA encoding interleukin (IL)-6, IL-8, IL-10, IL-12p19, IL-12p35, IL-12p40, IL-18, IFN-gamma, TNF-alpha, TGF-beta, eotaxin-2 and all four monocyte chemoattractant proteins (MCPs) relative to controls. LPR was associated with significantly increased expression of mRNA encoding IL-5, IL-8, IL-10, IL-12p19, IL12p40, IL-18, TNF-alpha, TGF-(3, MCP-2 and MCP-3 relative to controls. There was significantly more expression of mRNA encoding IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-18, IFN-gamma, TNF-alpha, TGF-(3 and all MCPs, and significantly less expression of IL-5 in dogs with SNA than in dogs with LPR. Thus, the profile of cytokine and chemokine gene expression in the nasal mucosa is different in dogs with LPR when compared to dogs with SNA. A partial Th2 immune response appears to be mounted in the nasal mucosa of dogs with LPR, whereas the mucosal immune response in canine SNA is of the Th1 type. Increase in IL-10 and TGF-(3 transcripts in dogs with SNA is thought to be implicated in the failure to clear the Aspergillus infection. These results constitute the first evidence that the pathogenesis of canine LPR and SNA is distinct. (C) 2007 Elsevier B.V All rights reserved.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Peeters, Dominique ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Médecine interne des animaux de compagnie
Peters, I. R.
Helps, C. R.
Gabriel, Alexandra
Day, M. J.
Clercx, Cécile ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Pathologie médicale des petits animaux
Language :
English
Title :
Distinct tissue cytokine and chemokine mRNA expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis
Burgener D.C., Slocombe R.F., and Zerbe C.A. Lymphoplasmacytic rhinitis in 5 dogs. J. Am. Anim. Hosp. Assoc. 23 (1987) 565-568
Clercx C., Peeters D., Snaps F., Hansen P., McEntee K., Detilleux J., Henroteaux M., and Day M.J. Eosinophilic bronchopneumopathy in dogs. J. Vet. Intern. Med. 14 (2000) 282-291
Elberg G., Elberg D., Logan C.J., Chen L., and Turman M.A. Limitations of commonly used internal controls for real-time RT-PCR analysis of renal epithelial-mesenchymal cell transition. Nephron Exp. Nephrol. 102 (2006) e113-e122
Gafa V., Lande R., Gagliardi M.C., Severa M., Giacomini E., Remoli M.E., Nisini R., Ramoni C., Di Francesco P., Aldebert D., Grillot R., and Coccia E.M. Human dendritic cells following Aspergillus fumigatus infection express the CCR7 receptor and a differential pattern of interleukin-12 (IL-12), IL-23, and IL-27 cytokines, which lead to a Th1 response. Infect. Immun. 74 (2006) 1480-1489
Hamilos D.L., and Lund V.J. Etiology of chronic rhinosinusitis: the role of fungus. Ann. Otol. Rhinol. Laryngol. Suppl. 193 (2004) 27-31
Hunter C.A. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat. Rev. Immunol. 5 (2005) 521-531
Johnson L.R., Drazenovich T.L., Herrera M.A., and Wisner E.R. Results of rhinoscopy alone or in conjunction with sinuscopy in dogs with aspergillosis: 46 cases (2001-2004). Am. Vet. Med. Assoc. 228 (2006) 738-742
Kolls J.K., and Linden A. Interleukin-17 family members and inflammation. Immunity 21 (2004) 467-476
Langrish C.L., McKenzie B.S., Wilson N.J., de Waal Malefyt R., Kastelein R.A., and Cua D.J. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol. Rev. 202 (2004) 96-105
Mackin A. Lymphoplasmacytic rhinitis. In: LG K. (Ed). Respiratory Diseases in Dogs and Cats (2004), Saunders, St Louis 305-310
Matsumoto N., Katoh S., Mukae H., Matsuo T., Takatsu K., and Matsukura S. Critical role of IL-5 in antigen-induced pulmonary eosinophilia, but not in lymphocyte activation. Int. Arch. Allergy Immunol. 130 (2003) 209-215
Montagnoli C., Fallarino F., Gaziano R., Bozza S., Bellocchio S., Zelante T., Kurup W.P., Pitzurra L., Puccetti P., and Romani L. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J. Immunol. 176 (2006) 1712-1723
Morrison B.E., Park S.J., Mooney J.M., and Mehrad B. Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J. Clin. Invest. 112 (2003) 1862-1870
Peeters D., Day M.J., and Clercx C. An immunohistochemical study of canine nasal aspergillosis. J. Comp. Pathol. 132 (2005) 283-288
Peeters D., Peters I.R., Farnir F., Clercx C., and Day M.J. Real-time RT-PCR quantification of mRNA encoding cytokines and chemokines in histologically normal canine nasal, bronchial and pulmonary tissue. Vet. Immunol. Immunopathol. 104 (2005) 195-204
Peeters D., Peters I.R., Clercx C., and Day M.J. Quantification of mRNA encoding cytokines and chemokines in nasal biopsies from dogs with sino-nasal aspergillosis. Vet. Microbiol. 114 (2006) 318-326
Peeters D., Peters I.R., Clercx C., and Day M.J. Real-time RT-PCR quantification of mRNA encoding cytokines, CC chemokines and CCR3 in bronchial biopsies from dogs with eosinophilic bronchopneumopathy. Vet. Immunol. Immunopathol. 110 (2006) 65-77
Peters I.R., Helps C.R., Calvert E.L., Hall E.J., and Day M.J. Cytokine mRNA quantification in histologically normal canine duodenal mucosa by real-time RT-PCR. Vet. Immunol. Immunopathol. 103 (2005) 101-111
Peters I.R., Helps C.R., Hall E.J., and Day M.J. Real-time RT-PCR: considerations for efficient and sensitive assay design. J. Immunol. Methods 286 (2004) 203-217
Peters I.R., Peeters D., Helps C.R., and Day M.J. Development and application of multiple internal reference (housekeeper) gene assays for accurate normalisation of canine gene expression studies. Vet. Immunol. Immunopathol. 117 (2007) 55-66
Ponikau J.U., Sherris D.A., Kephart G.M., Adolphson C., and Kita H. The role of ubiquitous airborne fungi in chronic rhinosinusitis. Clin. Rev. Allergy Immunol. 30 (2006) 187-194
Ponikau J.U., Sherris D.A., Kern E.B., Homburger H.A., Frigas E., Gaffey T.A., and Roberts G.D. The diagnosis and incidence of allergic fungal sinusitis. Mayo Clin. Proc. 74 (1999) 877-884
Richardson M.D., and Patel M. Stimulation of neutrophil phagocytosis of Aspergillus fumigatus conidia by interleukin-8 and N-formylmethionyl-leucylphenylalanine. J. Med. Vet. Mycol. 33 (1995) 99-104
Riechelmann H., Deutschle T., Rozsasi A., Keck T., Polzehl D., and Burner H. Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin. Exp. Allergy 35 (2005) 1186-1191
Roilides E., Sein T., Roden M., Schaufele R.L., and Walsh T.J. Elevated serum concentrations of interleukin-10 in non-neutropenic patients with invasive aspergillosis. J. Infect. Dis. 183 (2001) 518-520
Romani L. Immunity to fungal infections. Nat. Rev. Immunol. 4 (2004) 1-23
Rothenberg M.E., and Hogan S.P. The eosinophil. Annu. Rev. Immunol. 24 (2006) 147-174
Rudack C., Sachse F., and Alberty J. Chronic rhinosinusitis - need for further classification?. Inflamm. Res. 53 (2004) 111-117
Sanchez-Segura A., Brieva J.A., and Rodriguez C. T lymphocytes that infiltrate nasal polyps have a specialized phenotype and produce a mixed TH1/TH2 pattern of cytokines. J. Allergy Clin. Immunol. 102 (1998) 953-960
Scavuzzo M.C., Rocchi V., Fattori B., Ambrogi F., Carpi A., Ruffoli R., Manganelli S., and Giannessi F. Cytokine secretion in nasal mucus of normal subjects and patients with allergic rhinitis. Biomed. Pharmacother. 57 (2003) 366-371
Schroeder A., Mueller O., Stocker S., Salowsky R., Leiber M., Gassmann M., Lightfoot S., Menzel W., Granzow M., and Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol. Biol. 7 (2006) 3
Sheppard D. Transforming growth factor beta: a central modulator of pulmonary and airway inflammation and fibrosis. Proc. Am. Thorac. Soc. 3 (2006) 413-417
Shin S.H., Ponikau J.U., Sherris D.A., Congdon D., Frigas E., Homburger H.A., Swanson M.C., Gleich G.J., and Kita H. Chronic rhinosinusitis: an enhanced immune response to ubiquitous airborne fungi. J. Allergy Clin. Immunol. 114 (2004) 1369-1375
Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3 (2003) 133-146
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., Speleman, F., 2002. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3 (RESEARCH0034).
Windsor R.C., Johnson L.R., Herrgesell E.J., and De Cock H.E. Idiopathic lymphoplasmacytic rhinitis in dogs: 37 cases (1997-2002). J. Am. Vet. Med. Assoc. 224 (2004) 1952-1957
Windsor R.C., Johnson L.R., Sykes J.E., Drazenovich T.L., Leutenegger C.M., and De Cock H.E. Molecular detection of microbes in nasal tissue of dogs with idiopathic lymphoplasmacytic rhinitis. J. Vet. Intern. Med. 20 (2006) 250-256
Yang M., Hogan S.P., Mahalingam S., Pope S.M., Zimmermann N., Fulkerson P., Dent L.A., Young I.G., Matthaei K.I., Rothenberg M.E., and Foster P.S. Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity. J. Allergy Clin. Immunol. 112 (2003) 935-943
Zonderland J.L., Stork C.K., Saunders J.H., Hamaide A.J., Balligand M.H., and Clercx C.M. Intranasal infusion of enilconazole for treatment of sinonasal aspergillosis in dogs. J. Am. Vet. Med. Assoc. 221 (2002) 1421-1425
