Trimming Surface Sugars Protects Histoplasma from Immune Attack

Abstract

Dectin-1 is an essential innate immune receptor that recognizes β-glucans in fungal cell walls. Its importance is underscored by the mechanisms that fungal pathogens have evolved to avoid detection by this receptor. One such pathogen is Histoplasma capsulatum, and in a recent article in mBio, Rappleye's group presented data showing that yeasts of this organism secrete a β-glucanase, Eng1, which acts to prune β-glucans that are exposed on the fungal cell surface [A. L. Garfoot et al., mBio 7(2):e01388-15, 2016, http://dx.doi.org/10.1128/mBio.01388-15]. The trimming of these sugars reduces immune recognition through Dectin-1 and subsequent inflammatory responses, enhancing the pathogenesis of H. capsulatum.

FIG 1

The Eng1 β-glucanase enhances the virulence of Histoplasma capsulatum by reducing β-glucan exposure. (A) Upon inhalation by the mammalian host, H. capsulatum switches to a yeast morphotype and induces the production of a number of virulence factors. One of these is the β-glucanase Eng1, which is secreted from the yeast and acts to trim off excess β-glucans exposed on the surface of the cell. This helps to prevent recognition by Dectin-1 on leukocytes, resulting in reduced inflammatory responses and increased pathogenesis in infected animals. (B) In strains of H. capsulatum where Eng1 has been depleted, Dectin-1-mediated recognition of surface-exposed β-glucan leads to enhanced inflammatory responses and fungal clearance, significantly reducing the virulence of this pathogen.