Recognition of Cryptococcus neoformans by Pattern Recognition Receptors and its Role in Host Defense to This Infection.

Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. Most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by C. neoformans. However, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (AIDS), often suffer from disseminated infection into the central nervous system, leading to life-threatening meningoencephalitis. The recognition of pathogen-associated molecular patterns (PAMPs) by macrophages and dendritic cells plays an important role as the first line of host defense in the elimination of pathogens. Recently, numerous pattern recognition receptors (PRRs) that recognize these PAMPs have been identified. Also, the involvement of these PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), in cryptococcal infection has been analyzed. In particular, TLR9, NLR family pyrin domain-containing 3 (NLRP3), Dectin-2, mannose receptor (MR), and DC-SIGN have been found to recognize the DNA, cell wall components, intracellular polysaccharides, and mannoproteins, respectively. Future studies are expected to promote elucidation of the mechanisms of host immune response to C. neoformans, which will lead to the development of new vaccines and therapies for cryptococcal infection.