NK cell degranulation as a marker for measuring antibody-dependent cytotoxicity in neutralizing and non-neutralizing human sera from dengue patients

Sun, Peifang; Morrison, Brian J.; Beckett, Charmagne; Liang, Zhaodong; Nagabhushana, Nishith; An, Li; Porter, Kevin R.; Williams, M. C.

doi:10.1016/j.jim.2016.11.005

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…While ADE Abs might be predominantly specific to antigens on the surface of a viral particle, such as envelope and membrane (or pre-membrane) proteins, ADCC Abs may additionally target non-structural proteins. We have previously shown that infected DC-SIGN Raji cells express PrM and E antigens on the surface of infected cells 10 . We also detected surface expression of non-structural proteins using monoclonal Abs (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Our group recently reported that non-neutralizing sera from a group of endemic subjects previously infected with DENV can bind to the surface of infected cells and can lead to rapid NK cell degranulation 10 , demonstrating the existence of Abs, in the same sera, capable of triggering Ab-dependent cell cytotoxicity (ADCC). The critical role of ADCC in controlling infection has been extensively studied in HIV and influenza patients 11–15 .…”

Section: Introductionmentioning

confidence: 99%

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NK Cells Activated through Antibody-Dependent Cell Cytotoxicity and Armed with Degranulation/IFN-γ Production Suppress Antibody-dependent Enhancement of Dengue Viral Infection

Sun

Williams

Nagabhushana

et al. 2019

Sci Rep

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Antibody (Ab)-dependent enhancement (ADE) is a hypothesized mechanism of increased disease severity during secondary dengue virus (DENV) infection. This study investigates Ab-dependent cell cytotoxicity (ADCC) in counteracting ADE. In our system, DENV and DENV-immune sera were added to peripheral blood mononuclear cells (PBMCs), and ADE and NK cell activation were simultaneously monitored. ADE was detected in monocytes and a concurrent activation of NK cells was observed. Activated NK cells expressed IFN-γ and CD107a. IFN-γ was detected at 24 hours (24 h) followed by a rapid decline; CD107a expression peaked at 48 h and persisted for >7 days. Optimal activation of NK cells required the presence of enhancement serum together with ADE-affected monocytes and soluble factors, suggesting the coexistence of the counteractive ADCC Abs, in the same ADE-serum, capable of strongly promoting NK cell activation. The function of NK cells against ADE was demonstrated using a depletion assay. NK cell-depleted PBMCs had increased ADE as compared to whole PBMCs. Conversely, adding activated NK cells back into the NK-depleted-PBMCs or to purified monocytes decreased ADE. Blocking IFN-γ expression also increased ADE. The study suggests that under ADE conditions, NK cells can be activated by ADCC Abs and can control the magnitude of ADE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NK Cells Activated through Antibody-Dependent Cell Cytotoxicity and Armed with Degranulation/IFN-γ Production Suppress Antibody-dependent Enhancement of Dengue Viral Infection

Sun

Williams

Nagabhushana

et al. 2019

Sci Rep

Self Cite

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“…ADCC responses are part of the effector immune mechanisms triggered by several viral infections (6–9, 38–40), and they are in some cases a better correlate with protection than neutralizing antibodies (8, 41). Indeed, ADCC represents one of the bases for the protection conferred by non-neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

Peste des Petits Ruminants Virus Fusion and Hemagglutinin Proteins Trigger Antibody-Dependent Cell-Mediated Cytotoxicity in Infected Cells

et al. 2019

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The adaptive immune system utilizes multiple effector mechanisms to clear viral infections. Among those antibody-dependent cell-mediated cytotoxicity (ADCC) can help recognize and clear virus-infected cells. In the present work we evaluated ADCC contribution to immunity in two economically important viral diseases that affect ruminants: bluetongue and peste des petits ruminants. Immune sera obtained from sheep experimentally infected with bluetongue virus (BTV) serotype 8 or peste des petits ruminant virus (PPRV) IC'89 were used for this study. PPRV immune sera could bind to the surface of PPRV-infected ovine B cells while BTV immune sera was unable to bind to the surface of BTV-infected sheep cells but could recognize intracellular BTV antigens. BTV and PPRV immune serum ADCC potency was established using an ovine autologous cytotoxicity assay that employed an NK cell-enriched fraction as effector cells and a virus-infected B cell-enriched fraction as target cells. In this system, immune sera triggered ADCC against PPRV-infected cells, but not against BTV-infected cells. PPRV immune sera could recognize PPRV fusion and hemagglutinin proteins on the surface of transfected cells, and enhanced lysis of these cells in ADCC assays. This indicated that these viral antigens are natural ADCC targets during PPRV infection. The present work describes a novel effector immune mechanism against PPRV in the natural host that could contribute to virus clearance highlighting the importance of studying protective immune mechanisms to improve current vaccines by invoking all effector arms of immunity.

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“…). DENV‐specific ADCC correlates with cell surface expression of DENV antigens and serotype‐specific neutralizing Ab titres . Higher ADCC activity in pre‐secondary DENV‐3 infection plasma samples correlated with lower plasma viraemia levels not seen with pre‐secondary DENV‐2 infection plasma samples…”

Section: Interactions That Can Activate Nk Cellsmentioning

confidence: 97%

Defining the role of NK cells during dengue virus infection

Mathew

2018

Immunology

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In recent years, our understanding of the complex number of signals that need to be integrated between a diverse number of receptors present on natural killer (NK) cells and ligands present on target cells has improved. Here, we review the progress made in identifying interactions between dengue viral peptides presented on HLA Class 1 molecules with inhibitory and activating killer-like immunoglobulin receptors on NK cells, direct interactions of viral proteins with NK cell receptors, the involvement of dengue virus-specific antibodies in mediating antibody-dependent cell-mediated cytotoxicity and the role of soluble factors in modulating NK cell responses. We discuss findings of NK cell activation early after natural dengue infection, and point to the role that NK cells may play in regulating both innate and adaptive immune responses, in the context of our new appreciation of interactions of dengue virus with specific NK cell receptors. With a number of flavivirus vaccine candidates in clinical trials, how NK cells respond to attenuated dengue virus and subunit protein vaccine candidates and shape adaptive immunity will need to be considered.

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NK cell degranulation as a marker for measuring antibody-dependent cytotoxicity in neutralizing and non-neutralizing human sera from dengue patients

Cited by 16 publications

References 23 publications

NK Cells Activated through Antibody-Dependent Cell Cytotoxicity and Armed with Degranulation/IFN-γ Production Suppress Antibody-dependent Enhancement of Dengue Viral Infection

NK Cells Activated through Antibody-Dependent Cell Cytotoxicity and Armed with Degranulation/IFN-γ Production Suppress Antibody-dependent Enhancement of Dengue Viral Infection

Peste des Petits Ruminants Virus Fusion and Hemagglutinin Proteins Trigger Antibody-Dependent Cell-Mediated Cytotoxicity in Infected Cells

Defining the role of NK cells during dengue virus infection

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