Abstract
Cryptococcosis is a neglected fungal disease that causes many deaths annually, is primarily caused by Cryptococcus neoformans and Cryptococcus gattii species. They are environmental fungus that engages lung pneumonia and a severe systemic infection. The rising incidence of affected immunocompetent hosts, particularly by the aggressive Cryptococcus deuterogattii (R265), underscores the urgency to understand factors influencing its dissemination. The immunopathogenesis of R265 infection is incompletely understood. Therefore, we investigate the role of IL-22 and IL-23 cytokines during R265 cryptocococcosis. Our findings highlight the crucial role of IL-22 and IL-23 cytokines in lung barrier homeostasis, preventing excessive lung damage. IL-22 not only prevents neutrophil infiltration and IL-17A production but also facilitates eosinophil lung infiltration. Ultimately, this study contributes vital insights into the selective role of IL-22 and IL-23 cytokines in immune activation and tissue regulation during the aggressive R265 lung and systemic infection.