Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

Table 1 Mechanisms of immune cell response in hepatitis B virus reactivation

Immune cells	Mechanism of impairment	Outcomes	Ref.
Innate immune cell responses
Natural killer cells	Downregulation of activating receptors (NKp30, NKp46, and CD56dim), inhibitory cytokine production (IFN- and TNF-)	Reduced viral clearance, increased reactivation risk	[62,64]
Dendritic cells	Reduced antigen presentation (CD8+ CTLs), impaired cytokine (IL-12 and IL-18) production	Impaired antiviral response, increased viral persistence	[40,65]
Macrophages	Dysregulated cytokine secretion (IL-1β, IL-6, and TNF-α)	Altered immune balance, increased inflammation	[49]
Neutrophils	Impaired chemotaxis, reduced phagocytosis	Ineffective pathogen clearance, prolonged viremia	[55]
Adaptive immune cell responses
CD8+ T cells	Exhaustion (CD8+ T cells), reduced cytotoxic activity	Inadequate viral control, viral persistence	[66]
CD4+ T cells	Decreased help for B and CD8+ T cells	Impaired adaptive immune response	[67]
B cells	Altered antibody production	Reduced neutralizing antibodies, prolonged viremia	[68]
Regulatory T cells	Dysfunction, reduced suppression	Dysregulated immune response, increased inflammation	[69]

IL: Interleukin; CTL: CD8+ cytotoxic T lymphocyte; TNF-α: Tumor necrosis factor-alpha; IFN: Interferons.