Immunosuppressive effects of Amblyomma cajennense tick saliva on murine bone marrow-derived dendritic cells

Background: Dendritic cells (DCs) are professional antigen-presenting cells with vital roles in the activation of host immunity. Ticks are bloodsucking arthropods that secrete bioactive compounds with immunomodulatory properties via their saliva. It is known that some tick species modulate the biology of DCs with different intensities; however, studies on Amblyomma cajennense, the Cayenne tick, have not yet been performed, although this species is considered one of the most capable of modulating immune responses of different hosts. Methods: Engorged female ticks were stimulated with dopamine to induce salivation, and saliva was pooled. The effects of tick saliva on the biology of dendritic cells were assessed by examining DC differentiation, maturation, migration, cellular viability, cytokine production and expression of surface markers by flow cytometry and ELISA. Competitive enzyme immunoassays (EIA) were used to measure saliva prostaglandin-E-2 (PGE(2)). Statistical significance was determined by ANOVA followed by Tukey's post-test or by the Kruskal-Wallis test with the Dunns post-test. Results: In this work, we demonstrated that the presence of A. cajennense saliva to bone marrow cultures inhibit DC differentiation. This inhibition was not accompanied by inhibition or induction of stimulatory and co-stimulatory molecules such as MHC-II, CD40, CD80 or CD86. Immature and mature DCs that were pre-exposed to saliva showed reduced migration toward the chemokines RANTES and MIP-3 beta. This inhibition was associated to a reduced expression of CCR5 (the receptor for RANTES) or CCR7 (the receptor for MIP-3 beta) induced by the presence of saliva in the cultures. Tick saliva also inhibited IL-12p40, IL-6 and TNF-alpha in a concentration-dependent manner while potentiating IL-10 cytokine production by DCs stimulated with Toll-like receptor-4 ligand. Additionally, A. cajennense tick saliva inhibited the expression of CD40 and CD86 in mature DCs while potentiating the expression of PD-L1. PGE2 was detected as one of the constituents of saliva at a concentration of similar to 80 ng/ml, and we believe that most of the results reported herein are due to the presence of PGE(2). Conclusions: These results help to understand the tick-host interaction and demonstrate that A. cajennense ticks appear to have mechanisms for modulating host immune cells, including DCs.