IL-22 and IL-23 regulate the anticryptococcal response during Cryptococcus deuterogattii infection

Area of Science:

• Immunology
• Mycology
• Infectious Diseases

Background:

• Cryptococcosis, caused by *Cryptococcus* species, is a significant fungal infection with high mortality.
• The aggressive *Cryptococcus deuterogattii* (R265) strain increasingly affects immunocompetent individuals, necessitating a deeper understanding of its pathogenesis.
• The precise immune mechanisms governing R265 infection, particularly in the lungs, remain largely undefined.

Purpose of the Study:

• To investigate the specific roles of Interleukin-22 (IL-22) and Interleukin-23 (IL-23) in the context of *Cryptococcus deuterogattii* (R265) infection.
• To elucidate how these cytokines influence lung barrier function and immune cell dynamics during R265-induced cryptococcosis.
• To understand the immunopathogenesis of aggressive R265 infections and identify potential therapeutic targets.

Main Methods:

• Experimental infection model using *Cryptococcus deuterogattii* (R265).
• Analysis of cytokine levels (IL-22, IL-23, IL-17A) and immune cell populations (neutrophils, eosinophils) in lung tissue.
• Assessment of lung barrier integrity and tissue damage markers.

Main Results:

• IL-22 and IL-23 play a critical role in maintaining lung barrier homeostasis during R265 infection.
• IL-22 was found to inhibit neutrophil infiltration and IL-17A production in the lungs.
• IL-22 actively promoted eosinophil infiltration into the lungs, suggesting a complex regulatory role.

Conclusions:

• IL-22 and IL-23 are essential for regulating immune responses and preventing excessive lung damage in aggressive R265 cryptococcosis.
• These cytokines demonstrate a selective role in immune activation and tissue protection, distinct from broader inflammatory responses.
• Targeting IL-22 and IL-23 pathways may offer novel therapeutic strategies for managing severe fungal lung infections.