Human NK Cells Induce Neutrophil Apoptosis via an NKp46- and Fas-Dependent Mechanism

Thorén, Fredrik B.; Riise, Rebecca; Ousbäck, Jenny; Chiesa, Mariella Della; Alsterholm, Mikael; Marcenaro, Emanuela; Pesce, Silvia; Prato, Carola; Cantoni, Claudia; Bylund, Johan; Moretta, Lorenzo; Moretta, Alessandro

doi:10.4049/jimmunol.1102002

Cited by 97 publications

(95 citation statements)

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“…Thus, both normal and leukemic neutrophils, obtained from patients with chronic myeloid leukemia, can inactivate NK cells and trigger ROS-dependent parthanatic cell death in NK cells (28)(29)(30). By contrast, we have recently demonstrated that NK cells promote neutrophil apoptosis by Fas and NKp46-dependent mechanisms (8). Furthermore, recent interim reports from the European Stop Tyrosine Kinase Inhibitor Study and Stop Imatinib (STIM) trials, aiming at evaluating the possibility to stop tyrosine kinase inhibitor therapy in chronic myeloid leukemia, suggest that intact NK cell function is pivotal for a favorable outcome (31,32).…”

Section: Discussionmentioning

confidence: 99%

“…After sedimentation of erythrocytes, granulocytes and PBMCs were separated by density gradient centrifugation. Remaining erythrocytes were lysed in distilled water as described elsewhere (8). The purity of granulocytes was .97%, with ,1% contaminating monocytes.…”

Section: Isolation Of Human Leukocytesmentioning

confidence: 99%

“…NK cells were originally identified as large granular lymphocytes with capacity to kill malignant and virusinfected cells without prior sensitization (6), but in the last decade, several studies also point toward an immunoregulatory role of NK cells. The NK cell-mediated immunomodulation is, in part, conveyed by specifically directed cytotoxicity against immune cells, such as activated macrophages, immature dendritic cells (DCs), neutrophils, and T cells (7)(8)(9)(10). By contrast, activated NK cells produce cytokines, which trigger the upregulation of HLA molecules, costimulatory molecules, and chemokine receptors on DCs (9,11).…”

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confidence: 99%

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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Riise

Bernson

Aurelius

et al. 2015

The Journal of Immunology

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Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-γ production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Human Leukocytesmentioning

confidence: 99%

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confidence: 99%

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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Riise

Bernson

Aurelius

et al. 2015

The Journal of Immunology

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“…NK cells also induce neutrophil apoptosis via an NKp46-and Fas-dependent mechanism, 25 and this may be involved in the resolution of acute inflammation. In the present study, we demonstrated an unreported interaction between NK cells and neutrophils via a paracrine secretion of IL-10.…”

Section: Circulation Research February 14 2014mentioning

confidence: 99%

Lung Natural Killer Cells Play a Major Counter-Regulatory Role in Pulmonary Vascular Hyperpermeability After Myocardial Infarction

Yan

Hegab

Endo

et al. 2014

Circulation Research

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Rationale: Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and nichespecific roles in distinct organs. Objective:We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction. Methods and Results: Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosisfactor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice. by respective effector functions. NK cells are cytotoxic lymphocytes critical to the innate immune system that can differentiate and mature in the bone marrow, lymph node, spleen, tonsils, and thymus before entering the circulation. In contrast to NKT cells, NK cells do not express invariant T-cell antigen receptors, Pan T marker CD3, or surface immunoglobulin (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, and NK1.1 in mice. NK cells play a highly important role in the killing of tumors and cells infected by viruses, and can have specialized and niche-specific functions in distinct organs. Conclusions:In the present study, we sought to examine the roles of cardiac NK cells in the pathogenesis of LV remodeling after MI. Unexpectedly, depletion of NK cells from mice had little effect on LV remodeling after MI; however, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. Thus, we examined a mechanism for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after MI. MethodsAn expanded Materials and Methods section is available in the online Data Supplement. Results Genetic Ablation of NK Cells Exacerbated Cardiogenic Pulmonary Edema After MIWe used a mouse model of nonreperfused MI to examine the possible role of NK cells in the pathogenesis of cardiac remodeling after MI. A detailed temporal analysis of cellular infiltrate dynamics in the post-MI heart revealed an initial increase in the number of NK cells on day 3 after MI, to a peak on day 7 (Online Figure I). In this study, we took advantage of the NKDTR/EGFP transgenic mice that express enhanced green ...

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“…NK cells are involved in regulating the activation and apoptosis of inflammatory cells, such as neutrophils and eosinophils8910. Furthermore, NK cells play a role in the recognition and clearance of eosinophils in the airway of asthmatic mice11.…”

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confidence: 99%

Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis

Kim

Choi

Lee

et al. 2016

Sci Rep

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Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.

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Human NK Cells Induce Neutrophil Apoptosis via an NKp46- and Fas-Dependent Mechanism

Cited by 97 publications

References 49 publications

TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Lung Natural Killer Cells Play a Major Counter-Regulatory Role in Pulmonary Vascular Hyperpermeability After Myocardial Infarction

Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis

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