Abstract
The cell wall is a ubiquitous structure in the fungal kingdom, with some features varying depending on the species. Additional external structures can be present, such as the capsule of Cryptococcus neoformans (Cn), its major virulence factor, mainly composed of glucuronoxylomannan (GXM), with anti-phagocytic and anti-inflammatory properties. The literature shows that other cryptococcal species and even more evolutionarily distant species, such as the Trichosporon asahii, T. mucoides, and Paracoccidioides brasiliensis can produce GXM-like polysaccharides displaying serological reactivity to GXM-specific monoclonal antibodies (mAbs), and these complex polysaccharides have similar composition and anti-phagocytic properties to cryptococcal GXM. Previously, we demonstrated that the fungus Histoplasma capsulatum (Hc) incorporates, surface/secreted GXM of Cn and the surface accumulation of the polysaccharide enhances Hc virulence in vitro and in vivo. In this work, we characterized the ability of Hc to produce cellular-attached (C-gly-Hc) and secreted (E-gly) glycans with reactivity to GXM mAbs. These C-gly-Hc are readily incorporated on the surface of acapsular Cn cap59; however, in contrast to Cn GXM, C-gly-Hc had no xylose and glucuronic acid in its composition. Mapping of recognized Cn GXM synthesis/export proteins confirmed the presence of orthologs in the Hc database. Evaluation of C-gly and E-gly of Hc from strains of distinct monophyletic clades showed serological reactivity to GXM mAbs, despite slight differences in their molecular dimensions. These C-gly-Hc and E-gly-Hc also reacted with sera of cryptococcosis patients. In turn, sera from histoplasmosis patients recognized Cn glycans, suggesting immunogenicity and the presence of cross-reacting antibodies. Additionally, C-gly-Hc and E-gly-Hc coated Cn cap59 were more resistant to phagocytosis and macrophage killing. C-gly-Hc and E-gly-Hc coated Cn cap59 were also able to kill larvae of Galleria mellonella. These GXM-like Hc glycans, as well as those produced by other pathogenic fungi, may also be important during host-pathogen interactions, and factors associated with their regulation are potentially important targets for the management of histoplasmosis.
Highlights
Regardless of the species, all fungi possess a surrounding polysaccharide enriched cell wall that varies in composition and structural organization (Erwig and Gow, 2016; Gow et al, 2017)
We found that these surface and extracellular glycans of H. capsulatum (Hc) have similar functions to C. neoformans (Cn) GXM; as with Cn and other GXM-like displaying fungi, Hc surface glycans may be important for the immunomodulatory functions during the pathogenesis of histoplasmosis
Serological reactivity of H. capsulatum (Hc) and C. neoformans (Cn) isolated glycans was compared using a panel of mAbs against cryptococcal GXM
Summary
Regardless of the species, all fungi possess a surrounding polysaccharide enriched cell wall that varies in composition and structural organization (Erwig and Gow, 2016; Gow et al, 2017). The main structure shared by several human pathogenic species is composed of an inner layer of chitin, a water-insoluble polymer of N-acetyl-glucosamine units linked by b-1,4glycosidic bonds, and, just external to it, a layer of branched b1,3- or b-1,6-glucans (Gow et al, 2017). These fungal surface polysaccharides are pathogen-associated molecular patterns (PAMPs) that are efficiently recognized by pattern recognition receptors (PRRs) on the surface of innate immunity cells for the initiation of the immune response (Romani, 2011). Despite mechanical protection for the fungal cells, all of these components are involved in the fungal escape of the immune response, since they all can shield cells from immune recognition (Rappleye et al, 2007; Erwig and Gow, 2016; Gow et al, 2017)
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