Double-threshold model for pDC stimulation and its effect on the course of viral infections. (A) During acute infections or the acute phase of most chronic infections, pDCs are activated beyond the threshold at which they exert antiviral activity, but pDC stimulation is rapidly reduced to maintain APC activity in the absence of proapoptotic and antiproliferative mechanisms. This allows the development and preservation of efficient T-cell responses that clear or control the infection. (B) If pDC activation is not controlled at the end of the acute phase (as during HIV infection), antiproliferative and proapoptotic mechanisms are kept active and undermine the maintenance of memory T-cell responses, favoring viral persistence.