Читать книгу Vaccines for Older Adults: Current Practices and Future Opportunities - Группа авторов - Страница 26

Innate immune cells rely on intracellular sensors known as PRRs to recognize pathogen-associated molecular patterns. One such PRR induced during viral infection by recognition of 5′-triphosphate (5′-ppp) is the RIG-I which induces type 1 IFN to control viral infections. Recent studies of DCs detected lower levels of RIG-I from older human subjects [40], and monocytes from older subjects have significantly diminished IFN-α/β responses to RIG-I stimulation [25]. Total human PBMCs exhibit impaired IFN responses to 5′-ppp RNA transfection relative to younger controls 6 h after stimulation, although in this complex cell population responses were comparable after 24 h [93]. Studies of potential mechanisms mediating these age-associated findings revealed that monocytes from older adults exhibit decreased expression of the adaptor protein TRAF3 as a consequence of its increased proteasomal degradation with age, thereby impairing the RIG-I primary signaling pathway for type I IFNs. Monocytes from older adults also fail to effectively upregulate the interferon regulatory transcription factor IRF8, compromising their ability to participate in IFN induction through secondary RIG-I signaling [26]. Such RIG-I signaling defects in multiple cell types could likely contribute to increased risk for infection and morbidity and mortality from viral infections in the context of aging. As the innate immune system helps instruct appropriate responses of the adaptive immune system, these innate signaling defects may also contribute to impaired adaptive immunity and vaccine efficacy during aging.