Prostaglandin E2 in tick saliva regulates host cell migration and cytokine profile

Abstract

Ticks are obligate ectoparasites that suppress the host's responses by secreting immunomodulatory and anti‐inflammatory molecules in their saliva. Previously, we have shown that tick salivary constituents from Dermacentor variabilis have distinctive effects on macrophage and fibroblast migration. Since tick saliva contains a high concentration of prostaglandin E2 (PGE2), we examined the effects of tick saliva on IC‐21 macrophage and NIH3T3‐L1 fibroblast migration in the absence and presence of a PGE2 antagonist. Assessment of macrophage and fibroblast migration showed the saliva‐induced changes in migration are reversed by the receptor antagonist AH 6809. Tick saliva induces macrophages to secrete copious amounts of PGE2, and conditioned medium from these cells caused a PGE2 antagonist‐sensitive inhibition on fibroblast migration. Using a cytokine antibody array, we showed tick saliva decreases the secretion of the pro‐inflammatory cytokines regulated and normal T cell expressed and secreted (RANTES/CCL5), tumor necrosis factor‐alpha (TNF‐α), and soluble TNF Receptor I (sTNFRI), through a PGE2‐dependent mechanism mediated by cyclic adenosine monophosphate (cAMP). Saliva also had similar effects on lipopolysaccharide (LPS) stimulated macrophages. Our data indicate ticks use PGE2 to regulate the acitivities of macrophages and fibroblast, cells important in the wound healing response.