The Reciprocal Interaction of NK Cells with Plasmacytoid or Myeloid Dendritic Cells Profoundly Affects Innate Resistance Functions

Abstract

A reciprocal activating interaction between NK cells and dendritic cells (DC) has been suggested to play a role in the functional regulation of these cells in immunity, but it has been studied only using in vitro generated bone marrow- or monocyte-derived DC. We report that human peripheral blood plasmacytoid DC (pDC) and myeloid DC are necessary to induce NK cell function depending on the type of microbial stimulus. pDC and myeloid DC are required for strongly increased NK cytolytic activity and CD69 expression, in response to inactivated influenza virus or CpG-containing oligonucleotides and poly(I:C), respectively. Secreted type I IFN is required and sufficient for the augmentation of NK cell cytolytic activity in the coculture with pDC or myeloid DC, whereas CD69 expression is dependent on both type I IFN and TNF. In addition, in response to poly(I:C), myeloid DC induce NK cells to produce IFN-γ through a mechanism dependent on both IL-12 secretion and cell contact between NK cells and myeloid DC, but independent of type I IFN. IL-2-activated NK cells have little to no cytolytic activity for immature myeloid DC and pDC, but are able to induce maturation of these cells. Moreover, IL-2-activated NK cells induce, in the presence of a suboptimal concentration of CpG-containing oligonucleotides, a strong IFN-α and TNF production. These data suggest that the reciprocal functional interaction between NK cells and either pDC or myeloid DC may play an important physiological role in the regulation of both innate resistance and adaptive immunity to infections.

NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection

“…These results suggested that soluble factors from infected DCs might contribute to increasing CD69 expression by NK cells. Whereas addition of neutralizing anti-IL-12 or anti-IFN-␣ to the culture had no affect on CD69 expression (data not shown), a mixture of anti-type I IFNs reduced CD69 up-regulation, as previously observed (19). Although CD69 expression was further reduced by including Abs against type I IFNs, NKG2D, and NKp46 in the culture, complete abrogation of CD69 expression was never achieved.…”

“…NK cells are particularly implicated in defense against viral infections, which they provide through killing of infected cells and the production of cytokines, notably IFN-␥ (13)(14)(15). Although recent studies have emphasized the role of DCs in promoting adaptive immune responses to influenza (16 -18), less has been said of the part played by NK cells and NK-DC cooperation (19).…”

“…Neutralizing Abs for cytokines were as follows: anti-IL-12p40 (C8.6, 10 g/ml), anti-IFN-␥ (clone B27, 20 g/ml) (BD Biosciences), rabbit polyclonal anti-IFN-␣, sheep polyclonal anti-IFN-␤, and mouse monoclonal anti-IFN-␣␤ receptor mAb (PBL Biomedical Laboratories). The anti-IFN-␣, anti-IFN-␤, and anti-IFN-␣␤ receptor Abs were used at concentrations of 1.5, 1.5, and 2.5%, respectively, of the commercial preparation as described previously (19). To block nonspecific binding of the Abs to Fc receptors, cells were first incubated for 10 min with Fc-blocking reagent (Miltenyi Biotech) that contains human IgG.…”

Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

“…Another factor in HIV-1 disease progression and immune system dysfunction is related to excessive immune activation (47)(48)(49). In HIV-1 infection, dysregulation of inflammatory responses points to the importance of studying critical molecules such as COX-2, which contributes to the pathogenesis of diseases with uncontrolled or chronic inflammation (50,51).…”

Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

“…18 As a first defense, NK cells and other innate lymphocytes play an essential role in the inhibition of tumorigenesis, tumor growth, and tumor metastasis. [19][20][21] We and other researchers previously demonstrated that dendritic cell (DC) therapy increases the activation of NK cells against tumor cells [22][23][24] and that CD1d C cells loaded with invariant NKT cell ligand generate NKT cell-mediated protection against tumor cells. 25 Although there are reports in tumor-bearing mice of interactions between NK cells and various types of myeloid cells, i.e., DCs, macrophages, MDSCs, it is unclear whether NK cells influence the number or function of MDSCs.…”