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Dendritic cells (DCs) and the initiation of the adaptive immune response

T. cruzi increases expression of MHC-I, -II, and costimulatory molecules on myeloid DCs.92,93 Activated DCs are critical for inducing protective immune response by producing IL-12 to induce IFN-y release by CD41 and CD81 T cells.94 96 Cruzipain (see hereunder), HSP70,9 ,9 and Tc52 have been shown to activate DCs, while sialylated structures of T. cruzi limit their IL-12 response by engaging the inhibitory receptor Siglec-E.98 TLRs engagement on DCs is not absolutely required to develop a Th1 response to T. cruzi.94 Intracellular Ca21 mobilization is rather the activating signal of DCs.94,95 Ca21 mobilization is triggered by parasite entry into the cell as well as by bradykinin produced upon the action of the parasite protease cruzipain on kininogen.95 TLR-2 indirectly potentiates the bradykinin- dependent activation of DC.99 Macrophage migration inhibitory factor (MIF) and C5a (produced upon complement activation) also contributes to DC activation.100,101

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