Pulmonary Iron Limitation Induced by Exogenous Type I IFN Protects Mice from Cryptococcus gattii Independently of T Cells

Cryptococcus neoformans andCryptococcus gattii cause fatal infection in immunodeficient and immunocompetent individuals. While these fungi are sibling species,C. gattii infects very few AIDS patients, whileC. neoformans infection is an AIDS-defining illness, suggesting that the host response to HIV selectsC. neoformans overC. gattii . We used a viral mimic molecule (pICLC) to stimulate the immune response, and pICLC treatment improved mouse outcomes from both species. pICLC-induced action againstC. neoformans was due to activation of well-defined immune pathways known to deterC. neoformans , whereas these immune pathways were dispensable for pICLC treatment ofC. gattii . Since these immune pathways are eventually destroyed by HIV/AIDS, our data help explain why the antiviral immune response in AIDS patients is unable to controlC. neoformans infection but is protective againstC. gattii . Furthermore, pICLC induced tighter control of iron in the lungs of mice, which inhibitedC. gattii , thus suggesting an entirely new mode of nutritional immunity activated by viral signals.