Candida auris MNN1 contributes to human neutrophil evasion via mechanisms independent of β-glucan unmasking

Systemic Candida ( Candidozyma ) auris infections can have mortality rates up to 60%, and little is known about immune responses to this fungal pathogen. Neutrophils play a major role in immunity to many fungal pathogens, including Candida species. However, neutrophils internalize C. auris at a lower rate than C. albicans . We previously found that the C. auris cell wall mannan blocks access to β-glucan, an immunostimulatory motif. Here, we analyzed the immune-evasion properties of C. auris mannan separate from glucan masking. We generated eight mannosylation mutants and identified two with increased rates of phagocytosis by human neutrophils. One of these mutants, mnn1 Δ, did not exhibit increased exposure of β-glucan. Nuclear magnetic resonance analysis of mnn1 Δ mannan showed decreased α-1,3-mannose linkages and acid-labile side chains. These structural changes increased the affinity of human Dectin-2 and Mincle for mannans in vitro , and Fab blocking of Dectin-2 decreased human neutrophil phagocytosis of mnn1 Δ. Overall, our work provides insight into human neutrophil recognition of C. auris mannans and further understanding of mechanisms of immune evasion for this fungal pathogen.