Older adults are significantly more susceptible to influenza than younger individuals. With age, infections occur more frequently, and the disease course becomes more severe, reflected in the fact that more than 90% of influenza-related deaths occur in people over 65 years of age. The reason for this high mortality lies in immunosenescence – the aging of the immune system, which loses its ability to mount adequate responses to viral attacks.

Nasal epithelial cells are the primary targets of influenza viruses. They are the first to be infected and play a decisive role in activating innate immunity and regulating adaptive immune responses.

Researchers in the United States compared the responses of nasal epithelial cells to the influenza virus in older and younger individuals.

Study Design

The study included two groups of healthy participants:

  • The first group – young adults aged 20 to 27 years.
  • The second group – older adults aged 55 or older.

Nasal mucosal epithelial cells were collected from all participants.

Some cells were infected with the influenza A H3N2 virus at 33°C to reproduce the temperature of the nasal epithelium accurately. The remaining cells were left uninfected and served as a control group.

In parallel, the researchers cultured immune cells capable of detecting the influenza virus in epithelial cells.

The investigators compared viral particle counts across different cell groups, the number of dying epithelial cells, the degree of innate and adaptive immune activation, and the levels of freely circulating proteins that signal the onset of infection.

Results

Nasal epithelial cells from older individuals transitioned into an antiviral state much less effectively in response to viral infection than cells from younger individuals.

Upon infection, epithelial cells typically begin producing interferon molecules – signaling proteins that activate all antiviral defense systems. Interferon induces the synthesis of proteins that inhibit viral replication. In older individuals, levels of two critical antiviral proteins that block infection at an early stage were significantly reduced. These proteins are part of the innate immune system and are produced in cells stimulated by interferon.

The first protein – IFITM1 – prevents viral entry into epithelial cells by inhibiting fusion of the viral membrane with the host cell membrane and blocking release of viral genetic material. In older individuals, IFITM1 levels were 2.6 times lower than in younger participants.

The second protein – MX1 – suppresses viral genetic activity within the cell by acting at multiple stages of viral replication. First, it prevents the formation of the primary viral genetic material copy in the nucleus of infected cells. Second, it binds to the primary copy, preventing further replication. Third, it neutralizes newly formed viral particles and prevents their release from infected cells. Overall, the biological role of this protein has been described in earlier studies as “natural resistance to influenza virus.” In the present study, nasal epithelial cells from older individuals produced 1.3 times less MX1 protein than cells from younger participants.

In the next phase of the experiment, researchers examined how effectively adaptive immune cells recognized infected epithelial cells. Recognition of infected cells is a complex process involving multiple proteins produced by infected cells. For analysis, the researchers selected several protein classes that play key roles in alerting immune cells to infection. Some proteins identify viral peptide fragments, others transport these peptides, and still others present them to immune cells. In older individuals, levels of these antigen-presenting proteins were reduced by 1.4-2.1 times, depending on the protein type.

The researchers also measured inflammatory responses in infected epithelial cells from individuals of different ages. In older adults, nasal mucosal cells produced significantly higher levels of pro-inflammatory signaling proteins.

Thus, older individuals face a higher risk of severe influenza due to a combination of age-related changes:

  • Weakened antiviral defenses in nasal mucosal cells.
  • Reduced the likelihood that infected epithelial cells will be detected by adaptive immune cells.
  • Elevated levels of inflammation.

Conclusion

Older adults are significantly more susceptible to influenza, and the disease course is more severe than in younger individuals, associated with impaired antiviral immunity and increased inflammation. Older individuals produce lower levels of innate immune proteins that directly counter viral invasion at the earliest stages of infection. In addition, adaptive immune efficiency is reduced due to weaker synthesis of antigen-presenting proteins in infected cells.

References

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