is an encapsulated basidiomycete yeast that causes disseminating infections in immunocompromised hosts, especially those with AIDS. There are two varieties of C. neoformans
: C. neoformans
(Serotype D) and C. neoformans
(Serotype A). Both are ubiquitous in the environment and can be commonly isolated from avian excreta, soil and trees. Infection is thought to begin with the inhalation of airborne spores and epidemiological evidence suggests that exposure to Cryptococcus
early in life can produce a prolonged, asymptomatic, latent infection [1
]. Should an infected individual later become immunocompromised, the fungus can then spread from the lungs to the central nervous system to cause meningoencephalitis, which is uniformly fatal without rapid clinical intervention [2
The mechanism by which C. neoformans
achieves latency and persistence prior to dissemination from its primary site of infection in the lung remains poorly understood. Recent data have revealed an important role for macrophages in this process. Firstly, C. neoformans
shows a remarkable ability to survive and proliferate within host macrophages in vitro
]. Secondly, live cryptococci can be recovered from circulating monocytes in infected mice [5
]. Thirdly, recent studies by our group and others have demonstrated that C. neoformans
is able to escape from within macrophages by a novel expulsive mechanism [6
]. After the expulsion, both the host macrophage and the expelled C. neoformans
appear morphologically normal and continue to proliferate, suggesting that this process may represent an important mechanism by which pathogens are able to escape from phagocytic cells without triggering host cell death and thus inflammation.
These findings have led to the so-called "Trojan horse" hypothesis on dissemination of C. neoformans
, which proposes that cryptococci are engulfed by phagocytic cells at an early stage of infection and then trafficked by these host cells into distal tissues without being exposed to the full onslaught of the immune system [8
]. However, it is not known how cryptococci remain intracellular for prolonged periods prior to dissemination, given that the period of latency far exceeds the natural lifespan of a host macrophage.
Using timelapse microscopy, we now show that C. neoformans is able to undergo 'lateral transfer' between phagocytes, during which the pathogen moves directly from an infected cell to neighbouring uninfected cells. This mechanism may explain the ability of C. neoformans to remain latent within the host during long periods of asymptomatic persistence, as well as providing protection during dissemination from primary sites of infection.