TH17 AXIS ACTIVATION IN THE IMMUNE RESPONSE AGAINST CRYPTOCOCCUS DEUTEROGATTII IN THE SYSTEMIC EXPERIMENTAL INFECTION

Cryptococcosis is caused by Cryptococcus neoformans and Cryptococcus gattii, resulting in severe pneumonia and, in extreme cases, cryptococcal meningoencephalitis. While, C. neoformans infects immunocompromised individuals through opportunistic infections, C. gattii causes primary infections in healthy individuals. The expansion of C. gattii's range is largely due to favorable climates in warmer regions. The Th17 response, involving cytokines like IL-17, IL-22, and IL-23, is crucial for controlling pulmonary cryptococcosis. However, Cryptococcus spp. can impair this response, leading to inadequate infection control. Dysregulated IL-22 and IL-23 production may contribute, with IL-22 providing protection but potentially causing inflammation if overproduced, and IL-23 supporting the Th17 response. The hypervirulent strain C. deuterogattii (R265) induces higher IL-22 production compared to other strains. The hypothesis is that R265 disrupts the Th17 pathway, causing lung tissue damage and aiding fungal colonization. Methodology included infecting C57BL/6 mice with R265, divided into four groups: uninfected, wild-type, IL-22 knockout, and IL-23 knockout. Serum, spleen, lungs, brain, and mediastinal lymph nodes were collected at 8, 13, and 18 days post-infection and analyzed for CFU, histopathology, ELISA, and flow cytometry. IL-22 deficient mice showed greater susceptibility to R265, with uncontrolled fungemia and cryptococcal meningitis due to high brain fungal load. Poor fungal control in the lungs is dependent on IL-22 rather than IL-23, as IL-23 deficient mice did not exhibit uncontrolled fungemia. IL-22 deficient mice had increased Th17 activation and cellular recruitment in the lungs. The absence of IL-22 impairs lymphocyte and eosinophil migration to the lungs while increasing neutrophils and macrophages.Thus, IL-22 aids lymphocyte recruitment and regulates the blood-lung barrier, limiting systemic fungal spread and mitigating pathological conditions.