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  • American Society of Hematology  (9)
  • 1
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1056-1056
    Abstract: After red blood cells, platelets represent the most abundant cell lineage in blood, where they sentinel the vasculature and play crucial functions in haemostasis and the prevention of bleedings. Platelets also express a vast array of immune mediators and receptors, suggesting that they can also be regarded as tiny immune cells capable of the recognition of pathogens. Indeed, platelets express functional Toll-like receptors and are thought to actively participate to innate immunity. During severe cases of H1N1 influenza A virus infection, circulating platelets display markers of activation. The specific platelet activation triggers during Influenza infection remain however unknown. In this study, we incubated human platelets with H1N1 influenza A virus (IAV) and monitored platelet activation. We found that IAV is a highly potent inducer of de novo lipid mediators production and a trigger for the release of microparticles from platelets. This activation process takes place independently of the Toll-like receptor 4 and requires the presence of serum, pointing to the contribution of soluble factor(s) present in blood. We observed that the virus scaffolds with immunoglobulin G to form large immune-complexes (∼1micron in size) that activate platelets through the engagement of FcgRIIA. Accordingly, the serum of naïve mice housed in a pathogen-free facility is ineffective at initiating human platelet activation when incubated in the presence of IAV. Intrigued by the fact that all the tested human sera were capable of forming immune complexes with IAV, we hypothesized that significant antibody cross-reactivity between different influenza viruses was sufficient to promote the formation of virus-containing immune complexes. Using in vivo approaches, we found that the antibodies from H3N2 influenza virus-immunized mice generate immune complexes when put in presence of H1N1, activating human platelets and transgenic mouse platelets that express FcgRIIA. Taken together, our observations demonstrate that beyond their activities in haemostasis and innate immunity, platelets can also play a role during the active stage of adaptive immune responses against pathogens through FcγRIIa activation. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    American Society of Hematology ; 2019
    In:  Blood Vol. 133, No. 19 ( 2019-05-09), p. 2001-2002
    In: Blood, American Society of Hematology, Vol. 133, No. 19 ( 2019-05-09), p. 2001-2002
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 1998
    In:  Blood Vol. 92, No. 1 ( 1998-07-01), p. 291-299
    In: Blood, American Society of Hematology, Vol. 92, No. 1 ( 1998-07-01), p. 291-299
    Abstract: The role of neutrophils during Epstein-Barr virus (EBV) infection is not known. Disruption of the initial and nonspecific immune response may favor the spread of EBV infection. We have previously shown that EBV interacts with human neutrophils and modulates protein expression. In this study we have investigated the ability of EBV to infect neutrophils. Electron microscopy studies showed penetration of virus and its subsequent localization to the nucleus. The presence of viral genomes in isolated nuclei from neutrophils was also shown by polymerase chain reaction (PCR). Expression of viral transcripts like EBNA-2 (Epstein-Barr nuclear antigen-2) and ZEBRA (BamHI Z EBV replication activator) was not detected by reverse transcriptase (RT)-PCR, suggesting that EBV does not seem to establish a latent or a lytic infection in neutrophils. However, at 20 hours post-EBV infection, 77% of cells were apoptotic as compared to 22% in uninfected cell cultures, as evaluated by flow cytometry. This EBV-induced apoptosis was prevented by the addition of granulocyte-macrophage colony-stimulating factor to the cell cultures. Apoptotic cell death seems to implicate the Fas/Fas ligand (L) pathway, as reflected by an increase of Fas/Fas L expression on neutrophils treated with EBV and an increase of soluble Fas L, which may function in an autocrine/paracrine pathway to mediate cell death. Lastly, EBV genome was detected from neutrophils of infectious mononucleosis (IM) patients in contrast to neutrophils obtained from healthy EBV-seropositive donors. Our findings on the interactions of EBV with neutrophils will then provide new insights on the immunosuppressive effects associated with EBV infection.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1998
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 12 ( 2022-06-28), p. 3697-3702
    Abstract: Immune complexes form in systemic disorders such as rheumatological, autoimmune, and allergic diseases or in response to infections or medications. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccines have been associated with rare yet serious thrombotic complications in the brain due to the formation of immune complexes that activate platelets. There are currently no data visualizing the interplay of platelets with leukocytes and the brain vasculature endothelium in response to immune complexes. This is in part due to the absence of FcγRIIA in mice, a receptor for immune complexes implicated in these thrombotic incidents. Here, we describe and illustrate events at the cellular level that take place in the brain vasculature in response to systemic administration of surrogate immune complexes. We used Ly6gCre+/−::Rosa26-TdT+/−::CD41-YFP+/− mice expressing the FcγRIIA transgene and fluorescence in neutrophils and platelets. Using real-time videomicroscopy to capture high-velocity events in conjunction with unbiased computer-assisted analyses, we provide images and quantifications of the cellular responses downstream of FcγRIIA stimulation. We observed transient and stable platelet–neutrophil interactions, platelets forming thrombi, and neutrophil adhesion to blood vessel walls. This imaging approach in a quadruple transgenic animal model can be used for the study of the pathogenic roles of immune complexes in disease.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 2876449-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 123, No. 18 ( 2014-05-01), p. 2854-2863
    Abstract: In influenza-immune subjects, H1N1 influenza virus–containing immune complexes can activate platelets through FcγRIIA. H1N1 can also activate platelets through thrombin, independently of FcγRIIA, pointing to a role of coagulation in influenza infection.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 12 ( 2022-06-28), p. 3593-3605
    Abstract: Platelets are hyperactivated in coronavirus disease 2019 (COVID-19). However, the mechanisms promoting platelet activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood. This may be due to inherent challenges in discriminating the contribution of viral vs host components produced by infected cells. This is particularly true for enveloped viruses and extracellular vesicles (EVs), as they are concomitantly released during infection and share biophysical properties. To study this, we evaluated whether SARS-CoV-2 itself or components derived from SARS-CoV-2-infected human lung epithelial cells could activate isolated platelets from healthy donors. Activation was measured by the surface expression of P-selectin and the activated conformation of integrin αIIbβ3, degranulation, aggregation under flow conditions, and the release of EVs. We find that neither SARS-CoV-2 nor purified spike activates platelets. In contrast, tissue factor (TF) produced by infected cells was highly potent at activating platelets. This required trace amounts of plasma containing the coagulation factors FX, FII, and FVII. Robust platelet activation involved thrombin and the activation of protease-activated receptor (PAR)-1 and -4 expressed by platelets. Virions and EVs were identified by electron microscopy. Through size-exclusion chromatography, TF activity was found to be associated with a virus or EVs, which were indistinguishable. Increased TF messenger RNA (mRNA) expression and activity were also found in lungs in a murine model of COVID-19 and plasma of severe COVID-19 patients, respectively. In summary, TF activity from SARS-CoV-2–infected cells activates thrombin, which signals to PARs on platelets. Blockade of molecules in this pathway may interfere with platelet activation and the coagulation characteristic of COVID-19.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 2876449-3
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  • 7
    In: Blood Advances, American Society of Hematology, Vol. 5, No. 3 ( 2021-02-9), p. 635-639
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 2876449-3
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  • 8
    Online Resource
    Online Resource
    American Society of Hematology ; 1999
    In:  Blood Vol. 94, No. 12 ( 1999-12-15), p. 4210-4219
    In: Blood, American Society of Hematology, Vol. 94, No. 12 ( 1999-12-15), p. 4210-4219
    Abstract: Natural killer (NK) cells are large granular lymphocytes capable of efficient killing of virus-infected and tumor cells in a major histocompatibility complex-independent manner. The cytotoxic killing potential of NK cells can be modulated by a variety of factors, including cytokines such as interleukin-12 (IL-12), IL-15, and interferon (IFN). IL-15 also plays an important role in NK cell development and survival. Killing of virally infected cells by NK cells is likely to represent an important antiviral defense mechanism, especially during the early phase of infection when antigen-specific immunity has yet to be generated. In the present work, we studied the potential of IL-15 to act as a modulator of NK cell-mediated antiviral defense. Our results clearly indicate that IL-15 can curtail infections by 3 human herpesviruses: Herpes simplex virus type 1, Epstein-Barr virus, and human herpesvirus 6. The antiviral activity of IL-15 is dose-, time-, and NK cell-dependent. IL-15–treated NK cells showed an increased killing potential against a variety of cells, including virus-infected target cells. Lastly, using highly purified cell population, we report that IL-15 triggers the synthesis of IFN-γ from both CD4+ and NK cells, which can act in both autocrine and paracrine fashion to modulate NK cells cytotoxic potential. In conclusion, IL-15 is a cytokine that can contribute to the establishment of an antiviral state in 2 ways: first by increasing the killing ability of NK cells and second by stimulating the synthesis and secretion of IFN.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 1999
    In:  Blood Vol. 94, No. 12 ( 1999-12-15), p. 4210-4219
    In: Blood, American Society of Hematology, Vol. 94, No. 12 ( 1999-12-15), p. 4210-4219
    Abstract: Natural killer (NK) cells are large granular lymphocytes capable of efficient killing of virus-infected and tumor cells in a major histocompatibility complex-independent manner. The cytotoxic killing potential of NK cells can be modulated by a variety of factors, including cytokines such as interleukin-12 (IL-12), IL-15, and interferon (IFN). IL-15 also plays an important role in NK cell development and survival. Killing of virally infected cells by NK cells is likely to represent an important antiviral defense mechanism, especially during the early phase of infection when antigen-specific immunity has yet to be generated. In the present work, we studied the potential of IL-15 to act as a modulator of NK cell-mediated antiviral defense. Our results clearly indicate that IL-15 can curtail infections by 3 human herpesviruses: Herpes simplex virus type 1, Epstein-Barr virus, and human herpesvirus 6. The antiviral activity of IL-15 is dose-, time-, and NK cell-dependent. IL-15–treated NK cells showed an increased killing potential against a variety of cells, including virus-infected target cells. Lastly, using highly purified cell population, we report that IL-15 triggers the synthesis of IFN-γ from both CD4+ and NK cells, which can act in both autocrine and paracrine fashion to modulate NK cells cytotoxic potential. In conclusion, IL-15 is a cytokine that can contribute to the establishment of an antiviral state in 2 ways: first by increasing the killing ability of NK cells and second by stimulating the synthesis and secretion of IFN.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
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