Toll-like receptors 2, 4 and 7, interferon-gamma and interleukin 10, and programmed death ligand 1 transcripts in skin from dogs of different clinical stages of leishmaniosis
Ordeix, Laura (Ordeix i Esteve) (Universitat Autònoma de Barcelona. Hospital Clínic Veterinari.)
Montserrat-Sangrà, Sara (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Martínez-Orellana, P. (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Baxarias, Marta (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Solano Gallego, Laia. (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)

Data:	2019
Resum:	Background: Canine leishmaniosis (CanL) caused by Leishmania infantum can have several dermatological manifestations. The type of immune response elicited against the parasite appears to be at the basis for such clinical variability. Much of the work in CanL has focused on adaptive immune response and there are scarce data on the importance of the innate immune responses. Moreover, few studies have evaluated the immunological response in the cutaneous lesions in dogs naturally infected with L. infantum and with different degrees of disease severity, and no study has compared clinically-lesioned with normal-looking skin. Methods: We determined and compared the transcription of toll like receptors (TLRs) 2, 4 and 7, interferon gamma (IFN-γ), interleukin (IL) 10 and programmed cell death protein ligand (PD-L) 1 by real-time PCR in paired clinically-lesioned and normal-looking skin from 25 diseased dogs (mild disease-stage I (n = 11) and moderate to severe disease-stages II and III (n = 14) as well as in normal-looking skin from healthy dogs (n = 10) from a non-endemic area. We also assessed the association between the transcripts in clinically-lesioned and normal-looking skin of dogs with leishmaniosis with clinicopathological, immunological and parasitological findings. Results: Clinically-lesioned skin from mildly affected dogs was characterized by a significant upregulation of TLR2 (P < 0. 0001) and IL-10 (P = 0. 021) and downregulation of TLR7 (P = 0. 004) when compared with more severely affected dogs. Normal-looking skin of mildly affected dogs was characterized by a significant lower expression of TLR7 (P = 0. 003), IFN-γ(P < 0. 0001) and PD-L1 (P = 0. 001) when compared with more severely affected dogs. TLR2, TLR4, IL-10 and IFN-γupregulation in clinically-lesioned skin was correlated with lower disease severity while TLR7 upregulation was correlated with markers of disease severity. Upregulation of TLR7, IL-10, IFN-γand PD-L1 in normal-looking skin was correlated with disease severity. Conclusions: This study demonstrated different expression profiles of immune genes in clinically-lesioned and normal-looking skin among mildly and more severely affected dogs. These immunological conditions might favor the maintenance and replication of the parasite in the skin of more severely affected dogs.
Ajuts:	Ministerio de Economía y Competitividad AGL2012‑32498 Ministerio de Economía y Competitividad AGL2015‑68477
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Leishmaniosis ; Canine ; Leishmania infantum ; Skin ; Cytokine ; Toll‑like receptors ; Gene expression
Publicat a:	Parasites & vectors, Vol. 12 Núm. 1 (may 2019) , p. 575, ISSN 1756-3305

DOI: 10.1186/s13071-019-3827-7
PMID: 31806038

13 p, 1.3 MB

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