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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.
- Source :
-
Parasites & vectors [Parasit Vectors] 2017 Mar 13; Vol. 10 (1), pp. 123. Date of Electronic Publication: 2017 Mar 13. - Publication Year :
- 2017
-
Abstract
- Background: 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.<br />Results: 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.<br />Conclusions: 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.
- Subjects :
- Animals
Antibodies, Protozoan blood
Antigens, Protozoan pharmacology
Cytokines immunology
Dogs
Enzyme-Linked Immunosorbent Assay veterinary
Interleukin-6 biosynthesis
Interleukin-6 blood
Interleukin-6 immunology
Leishmaniasis, Visceral immunology
Lipopeptides immunology
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha blood
Tumor Necrosis Factor-alpha immunology
Antigens, Protozoan immunology
Cytokines blood
Dog Diseases immunology
Leishmania infantum immunology
Leishmaniasis, Visceral veterinary
Lipopeptides pharmacology
Toll-Like Receptor 2 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1756-3305
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Parasites & vectors
- Publication Type :
- Academic Journal
- Accession number :
- 28288677
- Full Text :
- https://doi.org/10.1186/s13071-017-2062-3