IFN-α and TRAIL: A double edge sword in HIV-1 disease?

IFN-alpha is rapidly upregulated in response to viral infections and it is an essential player in innate immunity against viruses. pDCs are the most potent IFN-alpha-producing cells and serve as an essential link between innate and adaptive immunity. The fate of pDCs in the course of HIV-1 infection is still a matter of debate, and the question of the detrimental role of chronic production of IFN-alpha remains open. In particular, IFN-alpha has been shown to induce the expression of the death ligand TRAIL on pDCs, transforming them into killer pDCs that may contribute to the destruction of CD4(+) T cells, the hallmark of HIV-1-induced disease. In this review, we discuss our current understanding of the protective and pathogenic roles of both IFN-alpha and TRAIL in HIV-1 disease. (C) 2012 Elsevier Inc. All rights reserved.