The old are more vulnerable to infectious disease as a result of the age-related decline of the immune system, but other mechanisms can also play a role. For example, leakage of the blood-brain barrier can allow pathogens access to the brain, a pathway not open in youth. Neurocryptococcosis is an example of an infectious condition of the central nervous system in which the pathogen is a fungus; it is more common in older people, and researchers here discuss why this is the case.
Neurocryptococcosis, an infectious disease of central nervous system (CNS) caused by Cryptococcus neoformans (C. Neoformans) and C. gattii, has been observed with increased frequency in aged people, as result of the reactivation of a latent infection or community acquisition. These opportunistic microorganisms belonging to kingdom of fungi are capable of surviving and replicating within macrophages. Typically, cryptococcus is expelled by vomocytosis, a non-lytic expulsive mechanism also promoted by interferon (IFN)-I, or by cell lysis. However, whereas in a first phase cryptococcal vomocytosis leads to a latent asymptomatic infection confined to the lung, an enhancement in vomocytosis, promoted by IFN-I overproduction, can be deleterious, leading the fungus to reach the blood stream and invade the CNS.
Although clinical evidence has pointed out the higher prevalence of neurocryptococcosis in older compared to younger adults, the exact mechanisms underlying this epidemiological evidence still need to be elucidated in depth. However, it is very plausible that age-related disruption of innate and acquired immune response may increase the risk of both cryptococcaemia and neurocryptoccocis and may enhance the direct deleterious effects of cryptococcal infection. Aging-induced defective clearing activity of alveolar macrophages, along with increased polarization into pro-inflammatory M1 cells and increased activation of Th2 responses, are thought to contribute to increased cryptococcal damage. Overall, age-associated alterations in innate immune responses may increase the risk of ineffective cryptococcal clearance, severe pulmonary disease, and dissemination to the CNS.
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