Efeitos imunossupressores da saliva de Amblyomma cajennense em células dendríticas derivadas de medula óssea murina

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells with essential roles in the activation of host immunity. Ticks are blood-sucking arthropods that secrete via saliva, bioactive compounds with immunomodulatory properties. It is known that some tick species modulate the biology of DCs with different intensities; however, studies with Amblyomma cajennense, the cayenne tick, have not yet been developed although this species is considered one of the most qualified for immunomodulation. In this work we demonstrated that the addition of A. cajennense tick saliva to bone marrow cells inhibits the differentiation to DCs. This inhibition was not accompanied by inhibition or induction of co- and stimulatory molecules MHC-II, CD40, CD80 and CD86. Immature or mature DCs pre-exposed to saliva showed reduced migration towards RANTES and MIP-3β chemokines, respectively. This inhibition was mediated by saliva which significantly reduced the expression of CCR5 or CCR7 chemokine receptors. Tick saliva also inhibited, in a concentration-dependent manner, IL-12p40, IL-6 and TNF-α while potentiating IL-10 cytokine production by DCs stimulated by Toll-like receptor-4 ligand. Additionally, the saliva was able to inhibit the expression of CD40 and CD86 in mature DCs while, per se, potentiating the expression of PD-L1. Prostaglandin-E2 was detected (~ 80 nM) as one of the constituents of saliva and we believe that some of the results obtained are due to their presence. Thus, these results help to understand the tick-host interaction and exemplify that ticks of the species A. cajennense seems to have particular mechanisms for modulation of host immune cells, including DCs.