Bidirectional NK/DC interactions promote CD4 expression on NK cells, DC maturation, and HIV infection

Interactions between natural killer (NK) and dendritic cells (DCs) are integral to immune response development, potentially leading to bidirectional NK/DC activation. We demonstrate that autologous NK/DC interactions induce CD4 expression on NK cells, influencing degranulation. Cell contact is required, with high NK:DC ratios and mature DCs most effectively inducing CD4 expression. CD4(+) NK cells, in turn, mediate DC maturation via contact-dependent and independent pathways, more effectively maturing DCs than CD4(-) NK cells. Bidirectional NK/DC interactions also impact HIV infection, as NK-matured DCs effectively deliver infectious HIV to T cells, via trans-infection. DC-induced CD4 expression also renders NM cells susceptible to HIV infection. Focusing on NM/DC interactions, DCs can transfer infectious virus and enhance HIV infection of CD4+ NM cells, strongly suggesting that these interactions influence HIV pathogenesis. Findings provide new insight regarding NM/DC interactions, defining a mechanism by which cellular interactions in the absence of pathogens promote DC-mediated amplification of HIV infection. (C) 2012 Elsevier Inc. All rights reserved.