Marco Colonna

..These data reveal key importance of FcRgamma-/-/CD3zeta-/- and thus maternal IgG during activation of mouse uNK cells and assign DAP12 but not DAP10 signaling contributions...

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..This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice...

..This introduction to the series brings together some of the novel concepts emerging from the experts' discussions...

..Whatever the ligands, targeted activation or blockade of TREM-1 and its ligands may help maximize the efficacy of existing treatments for sepsis...

..The meeting highlighted emerging themes in NK cell responses to viruses, NK cell tolerance and potential use of NK cells in the therapy of malignancies...

..But recent studies, including one in this issue, suggest that MHC class I-independent inhibitory signals can also result in inhibition of cytotoxic cells...

..The discovery of these immunosuppressive mechanisms provides new perspectives for the therapy of chronic infections associated with immunosuppression...

..Here we review recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases...

..Finally, we discuss the challenges faced in furthering our understanding of the developmental relationships and role of NK and LTi-like cells in mucosal immune responses...

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..In this issue, Hoeffel et al. (2007) show that human plasmacytoid dendritic cells can crosspresent HIV-derived peptides conjugated to a lipopeptide or HIV-infected cells undergoing apoptosis...

..These distinct TLR-IRF pathways may allow the immune system to tailor its responses to viral pathogens...

..Activated cells then secrete IFN-alpha and TNF-alpha, which trigger tissue release of chemokines that attract self-reactive CD8+ T cells, ultimately leading to liver damage...

..These breakthroughs have brought IPC to the attention of immunologists for their role in innate immunity and in shaping T cell responses. Here we review recent progress and outstanding questions in the field...

..DAP12 was essential for phosphorylation and nuclear accumulation of beta-catenin. Our results provide a mechanistic explanation for the many defects of DAP12-deficient mononuclear phagocytes...

..We conclude that DC and IPC are hard-wired to secrete IFN-alpha via different pathways, reflecting their complementary but distinct roles in anti-viral immunity...

..Taken together, these data show that TREM-2 is expressed on newly differentiated and alternatively activated macrophages and functions to restrain macrophage activation...

..Il34(LacZ/LacZ) mice selectively lacked LCs and microglia and responded poorly to skin antigens and viral infection of the CNS. Thus, IL-34 specifically directs the differentiation of myeloid cells in the skin epidermis and CNS...

..We conclude that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance...

..These results demonstrate distinct yet complementary roles for MDA5 and TLR3 in poly(I:C)-mediated NK cell activation...

..Based on these findings, we propose a novel model of ITAM-independent signaling by Vav downstream of DAP10 in NK cells...

..Thus, while many activating NK-cell receptors are promiscuous in terms of adaptor association, our data indicate that the functional consequences of such promiscuity may vary widely and may not be evident in all cases...

..Our data shed light on the multiple intersecting pathways through which PI3Ks control NK cell-mediated innate responses...

..These results demonstrate that PLCgamma2 is crucial for development of the NK cell receptor repertoire and signaling of activating NK cell receptors, mediating optimal NK cell function in vivo...

..These results provide new insights into the mechanism of immunological synapse formation and also demonstrate how multiple mechanisms can be used to recruit the same signaling proteins to the plasma membrane...

..In terms of function, expression of distinctive cell surface receptors, and location in lymphoid organs, NK1.1(+)B220(+)CD11c(+) appear to be the murine equivalent of human CD56(bright) NK cells...

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..We conclude that pDCs mediate early antiviral IFN-I responses and influence the accrual of virus-specific NK or CD8(+) T cells in a virus-dependent manner...

..These results reveal a novel molecular interaction that mediates adhesion of TFH to FDC and provide the first evidence that immune receptors for Nectins/Necl may be involved the generation of T cell-dependent antibody responses...

..IFN-I-mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases...

..Identification of the adhesive machinery required for IPC trafficking into PLNs may provide opportunities to regulate immune responses reliant on the activity of these cells...

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..Thus, DNAX-activating molecule-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection...

..Furthermore, they reveal Necl-2 as one of the molecular targets that allows the immunosurveillance network to distinguish tumor cells from normal cells...

..Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease...

..Finally, we discuss the emergent role of pDCs and one of their receptors, tetherin, in human immunodeficiency virus pathogenesis...

..We therefore conclude that optimal functioning of viral sensors and prompt IFN-I responses are required to prevent diabetes when caused by a virus that infects and damages the β cells of the pancreas...

..In this Viewpoint, we discuss how the recruitment and accumulation of pDC may impact pathogenesis of several diseases and how pDC can be targeted for therapeutic interventions...

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..Consequently, engagement of SIRPbeta2 on T cells by CD47 on antigen-presenting cells results in enhanced antigen-specific T-cell proliferation...

..These studies show that Trem2 signaling is an important pathway to promote healing of wounds in the colon where stem cell replacement is necessary...

..We conclude that MDA5 and TLR3 mediate substantially distinct yet complementary functions during poly I:C-mediated activation of Ag-specific CD8 T cell responses...

..We conclude that PLCgamma2 is a crucial signaling mediator that modifies DC gene expression program to activate DC responses to beta-glucan-containing pathogens...

..Finally, we show that BST2 resides within an intracellular compartment corresponding to the Golgi apparatus, and may be involved in trafficking secreted cytokines in IPC...

..Thus, effective antiviral CD8(+)T cell responses depend on the timing and magnitude of IFN-I production...

..These results reveal that TREM2 regulates the rate of osteoclastogenesis and provide a mechanism for the bone pathology in NHD...

..CONCLUSIONS: These data demonstrated a sepsis-specific transcriptional program that precedes sepsis-induced phenotypic changes in CD4+ splenocytes...

..Cumulatively, our data suggest that FcRLA plays a role in Ig assembly that can be compensated for by other proteins...

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..Moreover, it supports a model in which engagement of DNAX-activation protein 12 (DAP12)-associated receptors with antibodies or low avidity endogenous ligands interferes with TLR-mediated cellular activation...

..Remarkably, TREM2 deficiency leads to a severe disease that is characterized by bone cysts and demyelination of the central nervous system, which results in dementia, implying that the function of TREM2 extends beyond the immune system...

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..Thus, NKG2D is a versatile receptor that, depending on the availability of adapter partners, mediates costimulation in T cells and/or activation in NK cells...

..Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell-mediated mucosal immunity...

..Independent and coordinated control of T cell proliferation and differentiation would provide the immune system with greater flexibility in regulating immune responses...

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..Imaging studies showed that KSR1 is recruited to the immunological synapse during T-cell activation and that membrane recruitment of KSR1 is required for recruitment of active ERK to the synapse...

..Moreover, mda-5-/- mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 in vivo...

..These results indicate that NK cell-activating receptors require PKC- to generate sustained intracellular signals that reach the nucleus and promote transcriptional activation, ultimately inducing IFN-gamma production...

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..This review highlights aspects in which pDCs are unique in comparison to other antigen-presenting cells in regulating innate and adaptive immune responses...

..Therefore, IL-3-mediated induction of NKp44 on IPCs may be an important component of the ongoing crosstalk between the innate and adaptive immune response that allows memory CD8+ T cells to control the IPC response to virus...

..Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity...

..Upon pathogen encounter, IPC positioning within the lymph node may be further directed by CCR7 and IPC secretion of inflammatory chemokines may attract other IPC, promoting cluster formation in lymph nodes...

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..We here review current knowledge on these receptors, CD226, CD96 and CRTAM, and their role in tumor immunosurveillance...

..Immature bone marrow-derived DC also processed exogenous HEL. We conclude that the DC sets normally found in tissue show a scale of maturation features but even the most immature process and present peptides by MHC class II molecules...

..This highlights the complexity of the host antiviral response and how multiple cellular and molecular components balance protective versus pathological responses...

..As PVR is highly expressed in certain tumors, this receptor system may be critical for NK cell recognition of tumors...

..To study the mechanism, we examined the effects of GM-CSF in the dextran sulfate sodium (DSS)-induced acute colitis model. We hypothesized that GM-CSF may work through effects on dendritic cells (DCs)...

..Human CD4+ T cells that produce interleukin 22 are an essential component of skin defense and repair. New evidence shows that these T cells recognize CD1a-lipid complexes on Langerhans cells...

..These results demonstrate a critical role for TREM-2 in the differentiation of mononuclear myeloid precursors into functional multinucleated OCs...

..This review highlights the features that make pDC uniquely able to sense and respond to viral infection...

..These data demonstrate that, during sepsis, DAP12 signaling augments the response to microbial products, amplifying inflammation and contributing to mortality...

..This process occurs independently of B7.1 costimulation but is dependent on programmed death ligand 1 (B7-H1). This finding may have important implications for tolerance induction in transplantation...

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..How DCs integrate information from pathogens, tissues, and innate leukocytes for the induction of immune responses was presented at the second International Conference on Dendritic Cells at the Host-Pathogen Interface...

..Collectively, these findings illustrate the critical importance of inflammatory monocytes as a first line of defense in controlling intestinal pathogens...

..This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses...

..As a result, the dimeric TREM-1 most likely contains two distinct ligand binding sites...

..These data show a dynamic interaction between innate and adaptive human lymphocytes and emphasize the importance of studying interactions between immune components to understand the immune response as a whole...

..Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens...

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..Our data suggest that activation of TREM-1 on monocytes participates during the early-induced and adaptive immune responses involved in host defense against microbial challenges...

..Our results suggest a new immunomodulatory role for tissue infiltrating PDC, which may prime tumor-specific T cell responses and affect tumor growth via soluble factors...

..Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-alpha secretion...

..Thus, the chronic exposure to tumor cells expressing NKG2D ligand alters NKG2D signaling and may facilitate the evasion of tumor cells from NK cell reactions...

..The Src family pathway intersects the TLR9-MyD88 pathway by promoting the tyrosine phosphorylation of TLR9 and the recruitment of Syk to this receptor...

..Our work contradicts the function of DC-SIGN as a Trojan horse to facilitate HIV-1 infection; rather, it supports the function of DC-SIGN/R (a designation referring to both DC-SIGN and DC-SIGNR) as an antigen-capturing receptor...

..Furthermore, we showed that eosinophils express slam-associated protein. The demonstration that human eosinophils express a functional 2B4 receptor indicates a broader role for these cells in health and disease...

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..Collectively, the results are consistent with the postulate that environmental programming of decidual macrophages may be dictated in part by their proximity to soluble HLA-G-producing fetal cytotrophoblast cells...

..These data outline a novel role for Th2 cytokines in the regulation of innate immune responses through triggering receptors expressed on myeloid cells...

..These results may explain why melanoma cells grow despite the presence of infiltrating immune cells...

..These studies will help to design better anti-HIV-1 vaccines. ..

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..We also have detected a binding partner of TREM-1 (the TREM-1 ligand) and we propose to identify this molecule as it may serve as a novel target for the treatment of septic patients, ..

..We also have detected a binding partner of TREM-1 (the TREM-1 ligand) and we propose to identify this molecule as it may serve as a novel target for the treatment of septic patients, ..

..These findings also substantiate the physiological relevance of the proposed studies to clinical human cancer situations. ..

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