Successive tick infestations selectively promote a T-helper 2 cytokine profile in mice

Several studies have revealed that T lymphocytes and cytokines play a crucial role in determining the outcome of parasitic infections in terms of protective immunity. In this study we found that Rhipicephalus sanguineus tick saliva stimulates transforming growth factor-beta (TGF-beta), and reduces interleukin-12 (IL-12) secretion by cells from normal C3H/HeJ mice. Moreover, murine lymph node cells harvested 6 days after the fourth infestation with ticks presented an 82.4% decrease in their proliferative response to concanavalin A (Con A) compared with the response of control cells. In addition, lymph node cells cultured in the presence of Con A showed a T-helper 2-type (Th2-type) cytokine profile, represented by augmented IL-4 and IL-10 and TGF-beta. On the other hand, the IL-2, interferon-gamma (IFN-gamma) and IL-12 synthesis was significantly inhibited. These results indicate that ticks may modulate the host's immune response through saliva injection. Considering that C3H/HeJ mice develop no protective immunity to R. sanguineus infestation, our results suggest that tick-induced Th2-type cytokines and a decreased proliferative response probably lead the host to a susceptible state to both tick and tick-transmitted pathogens.