Study On Pathogenesis Of Cutaneous And Lung Cryptococcosis

Cryptococcus neoformans is one of pathogenic yeast, which could infect both immunocompromised, and immumocompetent host. The incidence of cryptococcosis has increased significantly during the past decades. Systems of host susceptible to Cryptococcus neoformans include skin, lung and central nerves system which is an life-threatening disease named cryptococcal meningitis. Lung and skin are not only the target of Cryptococcus neoformans , but also possible route for entre of Cryptococcus neoformans. Currently, study on pathogenesis of cryptococcosis is rare and limited in the function of immunity system.In the research on pathogenesis of skin cryptococcosis, we established the animal model of primary cutaneous cryptococcosis(PCC) through intravenous injection of different strains of Cryptococcus neoformans, which suggest that inoculation of pathogen after wound of skin may be one of disposing factor for PCC. After tracting the course of PCC in mice and comparing the immunity ststus on the infection, we observed that appearance of skin lesion is only related to the volume of injected Cryptococcus neoformans, which shows 10~7/ml or higher is sufficient. The lesion forms of skin PCC in mice are nodule, ulcer or molluscum-contagiosum like lesion. The ability to cause skin infection between variety gatti and variety neoformans of Cryptococcus neoformans, and between acapsuled isolate and encapsuled isolate are maybe the same Cryptococcus neoformans could infect both immunocompromised and immunocopetent mice , which suggest that PCC may present in bothimmunocompromised and immunocopetent host; however, immunocompromising status could promote dissemination of cryptococcal infection of skin.Interaction of Cryptococcus neoformans and human keratinocyte in vittro shows that Cryptococcus neoformans could adhere to, invade and get across keratinocyte and the layer of cells. The ability of adhere to and invade keratinocyte is higher in acapsuied isolate than in encapsuled isolates, while the apotosis rate of of keratinocyte is lower in in acapsuied isolate than in encapsuled isolates, which demostrate that capsule of Cryptococcus neoformans play an important role in damage keratinocyte , but counteract in adherence and invading of the cell. Two varieties of Cryptococcus neoformans shows similar effect on keratinocyte in adherence, invading and damage of the cell. After adhering to keratinocyte, Cryptococcus neoformans could induce tyrosine residue of membrane protein phospholization, which is the tyrosine protein kinase signal transduction pruduct. Inhibitory of TPK could significantly decrease invading rate of Cryptococcus neoformans to keratinnocyte, suggesting that TPK activation correlate to invading of Cryptococcus neoformans to keratinnocyte. Western blot demonstrate protein of 170 and 80Kd is specific of acapsuied isolate and maybe related to high rate of invading of the isolate..In the research on pathogenesis of lung cryptococcosis, we just focus on interaction of lung epithelial cell with Cryptococcus neoformans because the animal model of lung cryptococcosis has been investgated extensively. After co-culture of Cryptococcus neoformans and lung epithelial cell type-II, we found that the result is similar to that of Cryptococcus neoformans and keratinocyte. That is Cryptococcusneoformans could adhere to, invade and get across lung epithelial cell and the layer of cells. The ability of adhere to and invade lung epithelial cell is higher in acapsuled isolate than in encapsuled isolates, while the apotosis rate of of lung epithelial cell is lower in in acapsuled isolate than in encapsuled isolates, which demostrate that capsule of Cryptococcus neoformans play an important role in damage lung epithelial cell, but counteract in adherence and invading of the cell. Two varieties of Cryptococcus neoformans show similar effect on lung epithelial cell in adherence, invading and damage of the cell. After adhering to lung epithelial cell, although Cryptococcus neoformans could also induce tyrosine residue of membrane protein phospholization, but protein of 55, 80 and 118Kd are specific of acapsuled isolate and maybe related to high rate of invading of the isolate.In conclusion, we assumed that 1. Cryptococcus neoformans could infect immunocompetent host as the immnunocornpromised host, as long as with enough quatity of viable yeast. 2. acapsule or thin capsule isolates may be the Cryptococcus neoformans form of entry into the host, while enviroment in the host could induce enlargement of its capsule. Different serotypes of Cryptococcus neoformans may have similar pathogenesis. 3. Skin is an possible route of entry into other systems of Cryptococcus neoformans. 4. TPK may be specific for dissemination of Cryptococcus neoformans both at skin and at lung infection, inhibition of TPK may control the cryptococcal infection to primary site.