ABSTRACT
Cryptococcus neoformans is a fungal pathogen that kills almost 200,000 people each year and is distinguished by abundant and unique surface glycan structures that are rich in xylose. A mutant strain of C. neoformans that cannot transport xylose precursors into the secretory compartment is severely attenuated in virulence in mice, yet surprisingly is not cleared. We found that this strain failed to induce the non-protective T helper cell type 2 (Th2) responses characteristic of wild type infection, instead promoting sustained Interleukin (IL)-12p40 induction and increased IL-17A (IL-17) production. It also stimulated dendritic cells to release high levels of pro-inflammatory cytokines, a behavior we linked to xylose expression. Finally, we discovered that inducible bronchus associated lymphoid tissue (iBALT) forms in response to cryptococcal infection. Although iBALT formation is delayed upon infection with xylose-deficient cryptococci, it subsequently restricts infection. These studies demonstrate that cryptococcal infection triggers iBALT formation and elucidate the role of xylose in the modulation of host response to this fungal pathogen.