Cryptococcus neoformans Δsgl1 Vaccination Requires Either CD4+ or CD8+ T Cells for Complete Host Protection

<jats:p><jats:italic>Cryptococcus neoformans</jats:italic> is a fungal pathogen causing life-threatening meningoencephalitis in susceptible individuals. Fungal vaccine development has been hampered by the fact that cryptococcosis occurs during immunodeficiency. We previously reported that a <jats:italic>C. neoformans</jats:italic> mutant (Δ<jats:italic>sgl1</jats:italic>) accumulating sterylglucosides (SGs) is avirulent and provides complete protection to WT challenge, even under CD4<jats:sup>+</jats:sup> T cell depletion, an immunodeficient condition commonly associated with cryptococcosis. We found high levels of SGs in the lungs post-immunization with Δ<jats:italic>sgl1</jats:italic> that decreased upon fungal clearance. Th1 cytokines increased whereas Th2 cytokines concurrently decreased, coinciding with a large recruitment of leukocytes to the lungs. Depletion of B or CD8<jats:sup>+</jats:sup> T cells did not affect either Δ<jats:italic>sgl1</jats:italic> clearance or protection from WT challenge. Although CD4<jats:sup>+</jats:sup> T cell depletion affected clearance, mice were still protected indicating that clearance of the mutant was not necessary for host protection. Protection was lost only when both CD4<jats:sup>+</jats:sup> and CD8<jats:sup>+</jats:sup> T cells were depleted, highlighting a previously unexplored role of fungal-derived SGs as an immunoadjuvant for host protection against cryptococcosis.</jats:p>