Titel
Peripheral NK cell phenotypic alteration and dysfunctional state post hepatitis B subviral particles stimulation in CHB patients: evading immune surveillance
Autor*in
Mohamed A Selim
Botany and Microbiology Department, Faculty of Science, Al-Azhar University
Reda A. Suef
Botany and Microbiology Department, Faculty of Science, Al-Azhar University
Ebrahim Saied
Botany and Microbiology Department, Faculty of Science, Al-Azhar University
... show all
Abstract
Background: The relationship between chronic hepatitis B (CHB) infection and natural killer (NK) cell dysfunction is well-established, but the specific role of HBV viral antigens in driving NK cell impairment in patients with CHB remains unclear. This study investigates the modulatory effects of hepatitis B virus subviral particles (HBVsvp, a representative model for HBsAg) on the phenotypic regulation (activating and inhibitory receptors), cytokine production and cytotoxic potential of peripheral blood mononuclear cell-derived natural killer cells (PBMCs-derived NK cell), which contributes to NK cell dysfunction in CHB infection, potentially serving as an effective HBV immune evasion strategy by the virus.
Methods: NK cells were isolated from peripheral blood of patients with CHB (n=5) and healthy individuals (n=5), stimulated with HBVsvp. Subsequent flow cytometric characterization involved assessing changes in activating (NKp46 and NKG2D) and inhibitory (CD94) receptors expression, quantifying TNF-α and IFN- γ cytokine secretion, and evaluating the cytotoxic response against HepG2.2.15 cells with subsequent HBVsvp quantification.
Results: In CHB patients, in vitro exposure of PBMCs-derived NK cell with HBVsvp (represent HBsAg model) significantly reduced NK cell-activating receptors expression (P = 0.022), increased expression of CD94 + NK cells (p = 0.029), accompanied with a reduced TNF-α - IFN-γ cytokine levels, and impaired cytotoxic capacity (evidenced by increased cell proliferation and elevated HBVsvp levels in co-cultures with HepG2.2.15 cells in a time-dependent), relative to healthy donors.
Conclusion: These findings suggest that HBVsvp may induce dysfunctional NK cell responses characterized by phenotypic imbalance with subsequent reduction in cytokine and cytotoxic levels, indicating HBVsvp immunosuppressive effect that compromises antiviral defense in CHB patients. These data enhance our understanding of NK cell interactions with HBsAg and highlight the potential for targeting CD94 inhibitory receptors to restore NK cell function as an immunotherapeutic approach. Further clinical research is needed to validate these observations and establish their utility as reliable biomarkers.
Stichwort
chronic hepatitis B (CHB)HB subviral particles (HBVsvp)HbsAgnatural killer (NK) cellsNKp46 and NKG2D activating receptorsCD94 inhibitory receptorcytokineimmunotherapy
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Frontiers in Immunology
Band
15
ISSN
1664-3224
Erscheinungsdatum
2024
Publication
Frontiers Media SA
Erscheinungsdatum
2024
Zugänglichkeit
Rechte
Rechteangabe
© 2024 Selim, Suef, Saied, Abdel-Maksoud, Almutairi, Aufy, Mousa, Mansour and Farag
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