scholarly journals Free ISG15 as a dimer generates IL-1β-producing CD8α+ dendritic cells at the site of infection

2017 ◽  
Author(s):  
Anna Napolitano ◽  
Annemarthe G. van der Veen ◽  
Monique Bunyan ◽  
Annabel Borg ◽  
Svend Kjaer ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Independent Manner ◽  
Molecular Determinants ◽  
Live Parasite ◽  
Ifn Γ ◽  
Covalently Linked ◽  
First Time

AbstractISG15 is strongly induced after type I IFN stimulation producing a protein comprised of two ubiquitin-like domains. Intracellularly, ISG15 can be covalently linked and modify the function of target proteins (ISGylation). In addition, free unconjugated ISG15 can be released from cells. We found that ISG15 is released in the serum of Toxoplasma gondii infected mice early after infection in a type-I IFN independent manner. Once in the extracellular space, free ISG15 forms dimers and enhances the release of key cytokines involved in the immune response to the parasite: IL-12, IFN-γ, and IL-1β. Its action is dependent on an actively invading and replicating live parasite. ISG15 induces an increase of IL-1β later during infection by leading to increased IL-1β producing CD8α+ dendritic cells at the site of infection. Here, we define for the first time the molecular determinants of active free ISG15 and link ISG15 to IL-1β production by CD8α+ dendritic cells. Thus we define ISG15 as a novel secreted modulator of the cytokine response during Toxoplasma infection.

scholarly journals STING: a master regulator in the cancer-immunity cycle

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuanyuan Zhu ◽  
Xiang An ◽  
Xiao Zhang ◽  
Yu Qiao ◽  
Tongsen Zheng ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Negative Effects ◽  
Independent Manner ◽  
Adaptive Immune ◽  
Cancer Immunity

Abstract The aberrant appearance of DNA in the cytoplasm triggers the activation of cGAS-cGAMP-STING signaling and induces the production of type I interferons, which play critical roles in activating both innate and adaptive immune responses. Recently, numerous studies have shown that the activation of STING and the stimulation of type I IFN production are critical for the anticancer immune response. However, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For instance, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Moreover, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells. In this review, we focus on STING and the cancer immune response, with particular attention to the roles of STING activation in the cancer-immunity cycle. Additionally, the negative effects of STING activation on the cancer immune response and non-immune roles of STING in cancer have also been discussed.

scholarly journals Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-γ Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Caldarale ◽  
Mauro Giacomelli ◽  
Emirena Garrafa ◽  
Nicola Tamassia ◽  
Alessia Morreale ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Clinical Manifestations ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Reactive Protein ◽  
Cardiovascular Damage ◽  
Inflammatory Chemokines ◽  
Ifn Γ ◽  
Inflammatory Syndrome

BackgroundSARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).ObjectiveWith this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations.MethodsWe investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission.ResultsPatients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-γ. By contrast, we detected IFN-α in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-α, showed profound depletion of this subset in MIS-C, but not in COVID-19.ConclusionsOur results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C.

scholarly journals TLR ligands upregulate RIG‐I expression in human plasmacytoid dendritic cells in a type I IFN‐independent manner

2014 ◽  
Vol 92 (8) ◽  
pp. 671-678 ◽  
Author(s):  
Attila Szabo ◽  
Zoltan Magyarics ◽  
Kitti Pazmandi ◽  
Laszlo Gopcsa ◽  
Eva Rajnavolgyi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Type I Ifn ◽  
Independent Manner

scholarly journals Type I IFN innate immune response to adenovirus-mediated IFN-γ gene transfer contributes to the regression of cutaneous lymphomas

2007 ◽  
Vol 117 (10) ◽  
pp. 2834-2846 ◽  
Author(s):  
Mirjana Urosevic ◽  
Kazuyasu Fujii ◽  
Bastien Calmels ◽  
Elisabeth Laine ◽  
Nikita Kobert ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Transfer ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Cutaneous Lymphomas ◽  
Ifn Γ

scholarly journals Type I IFN Induces IL-10 Production in an IL-27–Independent Manner and Blocks Responsiveness to IFN-γ for Production of IL-12 and Bacterial Killing inMycobacterium tuberculosis–Infected Macrophages

2014 ◽  
Vol 193 (7) ◽  
pp. 3600-3612 ◽  
Author(s):  
Finlay W. McNab ◽  
John Ewbank ◽  
Ashleigh Howes ◽  
Lucia Moreira-Teixeira ◽  
Anna Martirosyan ◽  
...  
Keyword(s):  
Type I ◽  
Type I Ifn ◽  
Independent Manner ◽  
Bacterial Killing ◽  
Ifn Γ

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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