title: Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection.
abstract: Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model.
authors.affiliation: Royal Veterinary College, Pathology and Pathogen Biology, University of London, Hawkshead Lane, North Mymms, AL9 7TA, United Kingdom.
authors.forename: Shazia
authors.initials: S
authors.lastname: Hosein
authors.affiliation: Universitat Autònoma de Barcelona, LeishLAB-SAF, Departament de Farmacologia de Terapèutica i de Toxicologia, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Alhelí
authors.initials: A
authors.lastname: Rodríguez-Cortés
authors.affiliation: Royal Veterinary College, Pathology and Pathogen Biology, University of London, Hawkshead Lane, North Mymms, AL9 7TA, United Kingdom.
authors.forename: Damer P
authors.initials: DP
authors.lastname: Blake
authors.affiliation: Royal Veterinary College, Clinical Sciences and Services, University of London, Hawkshead Lane, North Mymms, AL9 7TA, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Allenspach
authors.affiliation: Universitat Autònoma de Barcelona, LeishLAB-SAF, Departament de Farmacologia de Terapèutica i de Toxicologia, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberola
authors.affiliation: Royal Veterinary College, Pathology and Pathogen Biology, University of London, Hawkshead Lane, North Mymms, AL9 7TA, United Kingdom; Universitat Autònoma de Barcelona, Facultat de Veterinaria, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Solano-Gallego
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D004285:Dogs; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000662:veterinary*; D009928:Organ Specificity / Q000235:genetics; D059208:Parasite Load; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D051858:Forkhead Transcription Factors; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors