Reciprocal Activating Interaction between Natural Killer Cells and Dendritic Cells

Gerosa, Franca; Baldani-Guerra, Barbara; Nisii, Carla; Marchesini, Viviana; Carrà, Giovanna; Trinchieri, Giorgio

doi:10.1084/jem.20010938

Cited by 919 publications

(931 citation statements)

References 23 publications

(20 reference statements)

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“…On the other hand, we demonstrated that IL-12 produced by IFN-g/FMKp-matured DC also augments NK-cell cytotoxicity toward the Raji cell line. This augmentation has been documented after contact of NK cells with some bacteria or by NK-DC crosstalk during bacterial infection [11,40].In conclusion, based on our in vitro data, it can be hypothesized that in vivo a K. pneumonia infection is responsible for induction of innate immune responses characterized by DC-dependent NK-cell migration, facilitating NK-DC interactions both in the periphery and in the lymphoid tissue. The molecular program triggered by FMKp and IFN-g does not only permit DC to recruit NK cells, but also induces the prerequisites necessary to activate NK-cell cytotoxicity and NK-cell helper function for Th1 polarization and possibly subsequent CTL induction.…”

supporting

confidence: 67%

Section: Discussionmentioning

confidence: 85%

“…This NK-induced DC maturation depends at least in part on soluble factors such as TNF-a [10] and IFN-g [11] as well as on engagement of the natural cytotoxicity triggering receptor 30 [12]. Moreover, NK cells control the quality of the adaptive immune response by natural cytotoxicity triggering receptor 30-mediated lysis of immature or inadequately matured DC [13], enabling only fully mature DC to migrate into lymph nodes and subsequently prime T cells.…”

Section: Introductionmentioning

confidence: 99%

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Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

et al. 2010

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Besides their role in destruction of altered self-cells, NK cells have been shown to potentiate T-cell responses by interacting with DC. To take advantage of NK-DC crosstalk in therapeutic DC-based vaccination for infectious diseases and cancer, it is essential to understand the biology of this crosstalk. We aimed to elucidate the in vitro mechanisms responsible for NK-cell recruitment and activation by DC during infection. To mimic bacterial infection, DC were exposed to a membrane fraction of Klebsiella pneumoniae, which triggers TLR2/4. DC matured with these bacterial fragments can actively recruit NK cells in a CCR5-dependent manner. An additional mechanism of DC-induced NK-cell recruitment is characterized by the induction of CCR7 expression on CD56 dim CD16 1 NK cells after physical contact with membrane fraction of K. pneumoniae-matured DC, resulting in an enhanced migratory responsiveness to the lymph node-associated chemokine CCL19. Bacterial fragment-matured DC do not only mediate NK-cell migration but also meet the prerequisites needed for augmentation of NK-cell cytotoxicity and IFN-c production, the latter of which contributes to Th1 polarization.Key words: CCR5 . CCR7 . NK-DC interaction . Th1 polarization Supporting Information available online Introduction NK cells are important effector cells in the innate immune response against virally infected or malignantly transformed cells and their cytotoxicity is regulated by a delicate balance of inhibitory and activating signals [1]. Recent studies suggest that the interplay between NK cells and DC, the specialized antigenpresenting cell of the innate immune system [2], is critical in shaping the adaptive immune response [3]. This concept originates from several lines of evidence including: the discovery of NK cells colocalizing with DC in the T-cell areas of lymph nodes [4,5], the coupling of NK-cell recruitment to lymph nodes Ã These authors contributed equally to this work. 3138with the induction of more potent Th1 skewing [3], and the identification of NK-cell subpopulations with helper properties [6]. Although the exact mechanisms of NK-DC interaction remain to be elucidated, increasing evidence supports the importance of bidirectional NK-DC crosstalk [7,8].On the one hand, NK-DC crosstalk is characterized by the capacity of activated NK cells to induce DC maturation with elevated IL-12p70 production and subsequently an increased capacity to induce Th1 and CTL responses [9]. This NK-induced DC maturation depends at least in part on soluble factors such as and as well as on engagement of the natural cytotoxicity triggering receptor 30 [12]. Moreover, NK cells control the quality of the adaptive immune response by natural cytotoxicity triggering receptor 30-mediated lysis of immature or inadequately matured DC [13], enabling only fully mature DC to migrate into lymph nodes and subsequently prime T cells. On the other hand, DC are able to induce NK-cell proliferation, augmentation of cytotoxicity and cytokine secretion [8]. The DC-induced modulati...

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supporting

confidence: 67%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

et al. 2010

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“…2,6,7 Specifically, NK cells have been implicated as having important reciprocal interactions with DC, facilitating collaboration between innate and adaptive immune responses. 4,5 In one carefully studied model of genetic immunization with adenovirally transduced DC that closely resembles our models, antitumor immunity was completely independent of CD8 þ T cells. 28,[40][41][42] When CD8 þ T cells were depleted using antibodies before or after immunization with AdVgp100-transduced DC, or when these DC were used to vaccinate CD8 genetically knockout mice, protection to a B16 tumor challenge was not impaired.…”

Section: Discussionmentioning

confidence: 93%

“…2 Subsequent studies have confirmed these observations in human in vitro cell cultures. [3][4][5][6][7] Additional studies focused on the possible role of NK cells in the activation of antigen-specific CTL responses generated by tumorantigen-loaded DC. Studies in both murine and human model systems showed that NK cells contributed to CTL generation.…”

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confidence: 99%

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

et al. 2005

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Tumor antigen gene-modified dendritic cells (DC) generates robust antigen-specific protective antitumor responses. Though the role of CD4 positive and CD8 positive cells in the immunological response to gene-modified DC has been well-characterized, the role of NK cells in this response has been somewhat less clear. Owing to the significant contribution of innate immunity in other model systems, we postulated that NK cells would hold a critical position in the generation of an immune response following immunization with tumor antigen-engineered DC. Immunization with MART-1 melanoma antigen-engineered DC in C57BL/6 mice resulted in the generation of antigen-specific cytotoxic T lymphocytes and in vivo protective responses to the murine B16 melanoma. These responses were dependent on the presence of functional NK cells, although NK cells alone were not sufficient in generating protective responses. Adoptive transfer of NK cells into an NK-deficient but T-cell-competent environment restored the protective response to gene-modified DC immunization. In conclusion, protective immunity after tumor antigen gene-modified DC immunization requires collaboration between CD4 þ and CD8 þ T cells and NK cells.

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Human Natural Killer Receptors, Co‐Receptors, and Their Ligands

Biassoni

Malnati

2009

CP in Immunology

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In the last 20 years, the study of human natural killer (NK) cells has moved from the first molecular characterizations of very few receptor molecules to the identification of a plethora of receptors displaying surprisingly divergent functions. Our laboratory has contributed to the description of inhibitory receptors and their signaling pathways, important in fine regulation in many cell types, but unknown until their discovery in the NK cells. Inhibitory function is central to regulating NK-mediated cytolysis, with different molecular structures evolving during speciation to assure its persistence. Only in the last ten years has it become possible to characterize the NK triggering receptors mediating natural cytotoxicity, leading to an appreciation of the existence of a cellular interaction network between effectors of both natural and adaptive immunity. This report reviews the contemporary history of molecular studies of receptors and ligands involved in NK cell function, characterizing the ligands of the triggering receptor and the mechanisms for finely regulating their expression in pathogen-infected or tumor cells.

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Reciprocal Activating Interaction between Natural Killer Cells and Dendritic Cells

Cited by 919 publications

References 23 publications

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

Human Natural Killer Receptors, Co‐Receptors, and Their Ligands

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