Effects of human immunoglobulins on Cryptococcus neoformans morphology and proteome

Cryptococcus neoformans (Cn) is the main cause of fungal meningitis (CM) in people living with HIV. Perturbations in levels of normal immunoglobulin (Ig) levels are observed in these individuals, but their association with CM pathogenesis is unclear. Here, we investigated the physical and biological effects of normal human immunoglobulins (not elicited by known cryptococcal infection), IgM, IgG, and IgA on Cn (strain H99). Each isotype affected the growth, surface morphology, and proteome of Cn. However, IgA had the most prominent effect. It induced growth inhibition after 24 h of co-culture with Cn, altered the structural organization of capsular fibers, and significantly reduced protein synthesis and proteins associated with intracellular glucuronoxylomannan (GXM) synthesis, such as those mediating transport of sugar precursors to Golgi and the cyclic AMP (cAMP) pathway. Together with prior data showing an association between reduced plasma IgA and HIV-associated CM, our findings suggest that the influence on human IgA on Cn pathogenesis warrants further investigation.