The spectrum of cutaneous manifestations in canine leishmaniosis: insights into diagnosis and immune responses
- Autores: Laura Ordeix Esteve
- Directores de la Tesis: Laia Solano Gallego (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Lluís Ferrer i Caubet (presid.), Alessandra Fondati (secret.), Ma. Magdalena Alcover Amengual (voc.)
- Programa de doctorado: Programa de Doctorado en Medicina y Sanidad Animales por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
The clinical variation observed in canine leishmaniosis (CanL) is determined by a variable immune response against the infection. Effective T helper 1 specific immune response is associated with control of parasite proliferation and disease progression. However, the role of innate immune response in instructing the polarization of the T helper response should not be ignored. Papular dermatitis, which in an endemic area is considered one typical manifestation of CanL, is the mildest cutaneous form of the disease.
The hypothesis of this doctoral thesis was that dogs with papular dermatitis as the sole clinical manifestation were dogs with a distinctive innate and adaptive immune response able to control disease progression in comparison with dogs with more severe cutaneous manifestations. It was also hypothesized that leishmanin skin test (LST) positive reaction in resistant dogs was histoimmunologically similar to papular dermatitis. The last hypothesis was that papular dermatitis may be more common in breeds known to be resistant to Leishmania infection.
Descriptive studies presented in the present doctoral thesis showed that papular dermatitis presented homogeneous clinicopathological pattern being the presence of papules, with the “volcanic” appearance, on sparsely haired skin in young dogs the most distinctive feature. Characteristically, dogs solely afflicted with this condition did not present clinicopathological abnormalities indicative of disease severity opposite with findings encountered in dogs with more severe cutaneous manifestations (chapters 4, 5 and 7).
In this doctoral thesis, new diagnostic results on canine papular dermatitis were found. Cytological examination with Leishmania-specific quantitative polymerase chain reaction (qPCR) on stained smears permitted the confirmation of the infectious nature of the papules in the majority of cases suggesting this combination technique as a promising diagnostic tool (chapter 5). Moreover, the histopathological studies showed that papular lesions were characterized by a nodular to diffuse pyogranulomatous dermatitis and granuloma formation with low parasite load demonstrated by means of Leishmania-specific qPCR. Moreover, normal-looking skin of dogs with papular dermatitis was less frequently inflamed and presented a lower parasite density than normal-looking skin of more severe sick dogs (chapters 3 and 4).
Chapters 4, 5 and 6 supported the adaptive immunological findings described previously in the literature for papular dermatitis and stage I leishmaniosis. In fact, a low or absent humoral immune response was documented in dogs with papular dermatitis while high antibody levels were found in dogs with exfoliative-ulcerative dermatitis. In addition, dogs with papular dermatitis showed a predominant cell-mediated immune response characterized by positive LST positive reactions. However, this doctoral thesis described for the first time, a high blood parasite specific IFN-γ production in dogs with papular dermatitis while an absent or reduced cell mediated immunity was found in dogs with more severe cutaneous manifestations (chapters 5 and 6). In addition, a significant slight agreement between LST, IFN-γ production and papular dermatitis was originally documented (chapter 5).
Papular dermatitis was more frequently diagnosed in young Ibizan hounds than in dogs belonging to other breeds in chapter 5.
The study described in chapter 6 demonstrated a distinct pattern of immune genes’ expression in the skin of dogs with papular dermatitis and stage I leishmaniosis compared with more severe sick dogs. Papules were characterized by higher TLR2, TLR4, IL-10 and IFN- transcripts whereas TLR7 was downregulated and PD-L1 transcript was similar in comparison with more severe cutaneous lesions. On the other hand, normal-looking skin from dogs with papular dermatitis presented lower expression of TLR2, TLR7, IL-10, IFN- and PD-L1 than more severe sick dogs whereas TLR4 transcript was similar among both groups. Although the nodular to diffuse pattern with granuloma formation was not observed in LST positive reactions, the analysis of the expression of the same immune genes showed a similar pattern of expression as found in papules (chapters 7 and 8).
In conclusion, this doctoral thesis demonstrated that dogs with papular dermatitis and stage I leishmaniosis presented a distinctive innate and adaptive immune response as well as clinicopathological and parasitological features when compared with more severe sick dogs that protects them against parasite proliferation and disease progression. In addition, a similar local immune response between papular lesions and LST positive reactions from resistant dogs was demonstrated, suggesting LST positive reactions as a surrogate of cutaneous lesions in dogs with a protective immunity. Furthermore, the higher frequency of papular dermatitis in young Ibizan hounds, suggests that the immunologic background of resistant dogs predisposes them to the development of papular dermatitis as the sole clinical sign of Leishmania infection.
