The inflammatory cytokine effect of Pam3CSK4 TLR2 agonist alone or in combination with Leishmania infantum antigen on ex-vivo whole blood from sick and resistant dogs
Martínez-Orellana, Pamela (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Quirola-Amores, Paulina (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Montserrat-Sangrà, Sara (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Ordeix, Laura (Ordeix i Esteve) (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Llull, Joan (Hospital Mon Veterinari)
Álvarez-Fernández, Alejandra (Clinica Veterinaria Noreña)
Solano Gallego, Laia (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)

Data:	2017
Resum:	A wide spectrum of clinical manifestations and immune responses exist in canine L. infantum infection. Ibizan hounds are more "resistant" to disease than other dog breeds. Recognition of pathogen-associated molecule patterns by toll like receptors (TLRs) rapidly triggers a variety of anti-microbial immune responses through the induction of pro-inflammatory cytokines such as TNF-α and IL-6 which may play an important role in controlling Leishmania infection. The main objective of this study was to investigate and compare the effect of a TLR2 agonist (TLR2a) alone or in combination with L. infantum antigen (LSA) on ex vivo whole blood cytokine production from healthy seronegative IFN-γ non-producer dogs from an area of low in canine leishmaniosis endemicity (n = 11); sick seropositive dogs with low production of IFN-γ (n = 17) and healthy seronegative or low positive Ibizan hounds with a predominant IFN-γ production (n = 21) from a highly endemic area. Whole blood was stimulated with medium alone (Ø), LSA, concanavalin A, TLR2 (Pam3CSK4) receptor agonist (Ø + TLR2a) and TLR2a and LSA (LSA + TLR2a) for 48 h. Supernatants were harvested for measurement of canine TNF-α and IL-6 cytokines by ELISA. A significant increase of TNF-α was found in the supernatants of stimulated blood from all groups (Ø + TLR2a and LSA + TLR2a) when compared with medium alone. A similar pattern was observed for IL-6. Interestingly, a significant increase of TNF-α production was only observed when stimulation with LSA + TLR2a was compared with TLR2a alone in Ibizan hounds. A significant increase of TNF-α production was observed with stimulation of LSA + TLR2a when compared with LSA in all groups. Significantly higher concentrations of TNF-α and IL-6 were detected in Ibizan hounds, especially for the Ø + TLR2a and LSA + TLR2a treatments compared with other groups. This study demonstrated that TLR2a alone enhances the production of the inflammatory cytokines TNF-α and IL-6 in sick, "resistant" and healthy non-infected dogs. In addition, a combination of LSA+TLR2a promoted a synergistic pro-inflammatory effect with TNF-α in Ibizan hounds but not in seropositive sick dogs and seronegative healthy dogs. These findings might suggest the importance of Pam3CSK4 as a possible immunomodulator for CanL. The online version of this article (doi:10. 1186/s13071-017-2062-3) contains supplementary material, which is available to authorized users.
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:	Ibizan hound ; Inflammatory cytokines ; Leishmania infantum ; Sick dog ; TLR-2 agonist (Pam3CSK4)
Publicat a:	Parasites & vectors, Vol. 10 (march 2017) , ISSN 1756-3305

DOI: 10.1186/s13071-017-2062-3
PMID: 28288677

7 p, 610.4 KB

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