The Innate Immune Cross Talk between NK Cells and Eosinophils Is Regulated by the Interaction of Natural Cytotoxicity Receptors with Eosinophil Surface Ligands

Abstract

Previous studies suggested that the cross talk between NK cells and other cell types is crucial for the regulation of both innate and adaptive immune responses. In the present study, we analyzed the phenotypic and functional outcome of the interaction between resting or cytokine-activated NK cells and eosinophils derived from non-atopic donors. Our results provide the first evidence that a natural cytotoxicity receptor (NCR)/NCR ligand-dependent cross talk between NK cells and eosinophils may be important to upregulate the activation state and the effector function of cytokine-primed NK cells. This interaction also promotes the NK-mediated editing process of dendritic cells that influence the process of Th1 polarization. In turn, this cross talk also resulted in eosinophil activation and acquisition of the characteristic features of antigen-presenting cells. At higher NK/eosinophil ratios, cytokine-primed NK cells were found to kill eosinophils via NKp46 and NKp30, thus suggesting a potential immunoregulatory role for NK cells in dampening inflammatory responses involving eosinophils.

Blood Eosinophilia Is an on-Treatment Biomarker in Patients with Solid Tumors Undergoing Dendritic Cell Vaccination with Autologous Tumor-RNA

“…A role for eosinophils as antigen-presenting cells (APC) was proposed several years ago [53]. More recently, evidence has indicated that the APC-like phenotype of eosinophils is influenced by NK-cells [29]. Eosinophils functionally interact with NK cells during the early phases of innate immune responses, participating in immune crosstalk.…”

“…Eosinophils functionally interact with NK cells during the early phases of innate immune responses, participating in immune crosstalk. They further improve NK cell's ability to induce DC editing and maturation [29]. Additional mechanistic studies will be critical to the understanding of the role played by eosinophils in cancer and vaccination.…”

“…Studies have suggested eosinophils to be part of an early inflammatory reaction at the site of tumorigenesis [27]. Eosinophils are not only a source of numerous cytokines and growth factors, but they also display both proinflammatory and anti-inflammatory activities, as well as immunoregulatory ones, which are most likely regulated by a complex network determined by surface molecules, extracellular components, and cell-cell interactions [28][29][30][31][32][33]. The role of eosinophils in allergic diseases led to several studies of the association between allergic conditions and cancer incidence [34,35].…”

Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

“…The isotype-specific goat anti-mouse was from Southern Biotechnology (Birmingham, AL, USA). For NCR ligand detection, NKp30-Fc NKp46-Fc were obtained as previously described (27)…”

Inhaled Kathon may induce eosinophilia‐mediated disease in the lung

“…While IgA stimulates the degranulation of eosinophils and basophils, IL‐12 inhibited degranulation and migration of eosinophils . Furthermore, some researchers suggested that NK cells can influence the innate and adaptive immune responses by regulating the activation and apoptosis of eosinophils . Therefore, we hypothesize that inhaled Kathon may induce eosinophilia in the lung by disrupting homeostasis of pulmonary surfactants.…”