Monocyte activation after influenza vaccination
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Monocyte Activation After Influenza Vaccination
Introduction to Monocyte Activation and Influenza Vaccination
Monocytes play a crucial role in the immune response to influenza vaccination. These cells, part of the innate immune system, can differentiate into various cell types, including dendritic cells and macrophages, which are essential for initiating and regulating immune responses. Understanding how monocytes are activated following influenza vaccination can provide insights into vaccine efficacy and potential areas for improvement.
Proinflammatory Cytokine Production in Monocytes
After influenza vaccination, there is a notable induction of proinflammatory cytokines in monocytes. Both young and older adults show an increase in CD14(+)CD16(+) inflammatory monocytes post-vaccination. These cells produce significant amounts of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are crucial for mounting an effective immune response. However, older adults exhibit a diminished cytokine response compared to younger individuals, which may contribute to their reduced vaccine efficacy.
Role of Interleukin 10 (IL-10) in Older Adults
In older adults, there is a marked elevation of the anti-inflammatory cytokine IL-10 in monocytes both before and after vaccination. This dysregulation of IL-10 production is associated with impaired vaccine responses, suggesting that IL-10 may play a role in the reduced efficacy of influenza vaccines in the elderly population.
Expression of Costimulatory Molecules CD80 and CD86
The expression of costimulatory molecules CD80 and CD86 on monocytes is critical for effective vaccine responses. Studies have shown that older adults have a significantly reduced increase in TLR-induced CD80(+) monocytes compared to younger adults. This reduction is associated with a lower vaccine response, indicating that the expression of these molecules can predict the efficacy of the influenza vaccine.
Epigenomic and Transcriptional Changes in Monocytes
Influenza vaccination induces persistent epigenomic changes in monocytes, such as diminished H3K27ac, which is associated with impaired cytokine responses to Toll-like receptor stimulation. These changes highlight the role of the epigenome in modulating immune responses and suggest that certain vaccines, like the AS03-adjuvanted H5N1 pandemic influenza vaccine, can induce beneficial epigenomic remodeling, enhancing antiviral gene expression and resistance to other viruses.
Monocyte-Derived Dendritic Cells (moDCs) and CD8+ T-Cell Activation
Monocyte-derived dendritic cells (moDCs) play a pivotal role in the immune response to influenza infection. These cells are crucial for the late activation of CD8+ T cells and the switch in immunodominance of the CD8+ T-cell response. The recruitment and activation of moDCs are essential for effective host resistance to secondary influenza challenges, underscoring their importance in vaccine design.
Pleiotropic Effects and Trained Immunity
Influenza vaccination can induce nonspecific or pleiotropic effects, such as the upregulation and downregulation of cytokines and epigenetic reprogramming in monocytes. This phenomenon, known as "trained immunity," involves the imprinting of an immunological memory in the innate immune system, which can enhance responses to subsequent infections.
Conclusion
Monocyte activation following influenza vaccination involves a complex interplay of proinflammatory and anti-inflammatory cytokines, costimulatory molecule expression, and epigenomic changes. These factors collectively influence the efficacy of the vaccine, particularly in older adults. Understanding these mechanisms can guide the development of more effective vaccines and therapeutic strategies to enhance immune responses across different age groups.
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