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

AbstarctInteractions 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 NK cells susceptible to HIV infection. Focusing on NK/DC interactions, DCs can transfer infectious virus and enhance HIV infection of CD4+ NK cells, strongly suggesting that these interactions influence HIV pathogenesis. Findings provide new insight regarding NK/DC interactions, defining a mechanism by which cellular interactions in the absence of pathogens promote DC-mediated amplification of HIV infection.

► Autologous DCs induce CD4 expression on NK cells in a cell-contact dependent manner. ► Co-culture with CD4+ NK cells results in DC maturation. ► CD4+ NK cell co-culture increases the DCs capacity to transfer virus and enhance HIV infection. ► Induction of CD4 expression by DCs renders NK cells susceptible to HIV-1 infection. ► DCs transfer infectious virus to CD4+ NK cells, enhancing CD4+ NK cell infection.