Eosinophils as an unexpected protector cellular component in a lethal mouse model of cryptococcosis triggered by C. gattii infection

Cryptococcosis is a systemic invasive mycosis responsible for nearly 625,000 deaths annually. Cryptococcus neoformans and C. gattii are its main etiological agents, with lungs as the primary site of infection. Eosinophils are prominent cells in bronchopulmonary cryptococcosis; however, their role in these fungal infections remains underexplored. Previous work has shown that pulmonary infection with C. gattii induces a type 2 immune response characterized by robust eosinophilia. We hypothesized that eosinophils play a central role in the immune response induced by C. gattii. To investigate this, BALB/c wild-type (WT) and eosinophil-deficient (ΔdblGATA-/-) mice were intratracheally inoculated with 10⁴ C. gattii yeasts. Infected WT mice exhibited intense eosinophilic infiltration in lung tissue and bronchoalveolar lavage (BAL). Notably, apart from the absence of eosinophils, ΔdblGATA-/- mice displayed a cellular infiltration profile comparable to that of WT animals, whose BAL eosinophils displayed signs of activation, evidenced by prominent content of cytoplasmic lipid body organelles. Like the susceptible C57BL/6 strain, ΔdblGATA-/- mice were more vulnerable to infection, displaying higher clinical scores and mortality rates than WT BALB/c mice. Approximately two weeks after infection, ΔdblGATA-/- mice exhibited earlier fungal dissemination to the brain than WT BALB/c mice. Note, in the absence of eosinophils, the infection also elicited earlier inflammatory ocular alterations. In vitro, human eosinophils (isolated from the peripheral blood of healthy donors) were directly activated by C. gattii or its purified capsular components, as evidenced by increased intracellular lipid body formation, whereas no DNA trap release was induced. Although additional studies are still required, these findings suggest that eosinophils exert a protective role during pulmonary C. gattii infection in BALB/c mice. (CEUA: A17/26 - A51-24-092-21)