Innate and Acquired Immunity in Cryptococcus neoformans Infections of the Central Nervous System

Abstract

Cryptococcus neoformans is an encapsulated yeast that causes cryptococcosis, a life-threatening disease that develops following inhalation and dissemination
of the ubiquitous organisms. C. neoformans has a predilection for the CNS, and mortality is most frequently associated with meningoencephalitis. Individuals with deficiencies
in cell-mediated immunity, such as AIDS patients, are more susceptible to cryptococcosis; thus, the incidence of cryptococcosis
is increasing as a result of the growing number of immunocompromised individuals. Loss of CD4+ T cells predisposes individuals to progressive infection with C. neoformans, further emphasizing the importance of cell-mediated immunity in host resistance to this organism and partially explaining
the high incidence of cryptococcosis in AIDS patients. Although much has been learned about host defense mechanisms against
C. neoformans in the lungs, less is known about host resistance in the CNS. Clearly, some of the same cells and mechanisms are involved
in host defense in the lungs and the CNS; however, the CNS has unique features that suggest there might be some differences
as well. In fact, experimental evidence indicates that many anticryptococcal reactions in the CNS are delayed in comparison
to extracerebral tissues, which may be due to differences in immune mechanisms in the CNS compared to other tissues. More
defined experimental studies are required to identify the critical components needed for appropriate anticryptococcal activity
in the CNS that restricts growth of C. neoformans while at the same time does not cause harmful damage to the nervous tissue.