Study On The Function And Mechanism Of Inflammatory Body In The Control Of Cryptococcal Capsular Mutant Infection

Innate immunity is a first line of the immune system, capable of mounting specific host responses against distinct pathogens. An integral component of the innate immune system is a network of pathogen recognition receptors, which are present at the surface of the cell or in the cytoplasm. Nucleotide oligomerization domain(Nod)-like receptors form the largest known family of intracellular innate immune sensors of microbes and danger signals that initiate early host responses. Some Nod-like receptors, such as NALP, NAIP and NLRC4, form molecular machines termed inflammasomes. Recerently,several inflammasomes had been identified to be involved in anti-fungi immunity and pathogens also evoluted various strategies to envade host immunity. Inflammasome as a component of innate immunity also involved in the process.Cryptococcus is a pathogen fungi addicted to the central nervous system but also infects the other organs such as lung skin and so on. The fungi mainly infected with AIDS patients and other immunocompromised patients with a high mortality rate. Although cell surface receptors for recognition of C. neoformans have been studied intensively, cytoplasmic recognition of this pathogen remains unclear. As an important detector of pathogen infection, inflammasome can sense and get activated by infection of various pathogens, including pathogenic fungi such as Candida albicans and Aspergillus fumigatus. Our present study showed that acapsular C. neoformans cap59D activated the NLRP3-, but not AIM2- nor NLRC4- inflammasome. During this process, viability of the fungus was required. Moreover, our in vivo results showed that during the pulmonary infection of cap59D, immune cell infiltration into the lung and effective clearance of the fungus were both dependent on the presence of NLRP3 inflammasome. In order to find the factor cap59D used to interaction with NLRP3 inflammasome,we also do experiment for further study. The result indicated that the RNA of acapsular C. neoformans cap59D may be a good choice.