A glucosylceramide from Lomentospora prolificans induces a differential production of cytokines and increases the microbicide ability of macrophages

Lomentospora prolificans (formely Scedosporium prolificans) is an opportunistic pathogen, responsible for serious infections in immunocompetent as well as immunocompromised patients, due to its high virulence and antifungal multidrug resistance. The cell wall glycoconjugates of the Pseudallescheria/Scedosporium complex have been studied extensively to identify the structures that are critical for fungal physiology and pathogenesis. Glucosylceramides (GlcCer) are the main neutral glycosphingolipids expressed in fungal pathogens. GlcCer are bioactive molecules in fungal cells and have several distinct roles. They are associated with fungal growth and morphological transitions in Cryptococcus neoformans, P. boydii, Candida albicans, Aspergillus fumigatus and Collectotrichum gloeosporioides
Anti-GlcCer Mab protects mice against lethal C. neoformans infection. Synergistic in vitro interactions were observed between the Mab against GlcCer and both amphotericin B and itraconazole and suggest the combined use of monoclonal antibodies against GlcCer and antifungal drugs for antifungal immunotherapy. More recently, structural analysis of GlcCer from three strains of Scedosporium (Pseudallesccheria) boydii, one strain of P. ellipsoidea and a P. augusta strain were carried and no differences were observed in the GlcCer structure.
Thus a conserved GlcCer structure similar to that previously described for S. apiospermum, S. aurantiacum and P. minutispora is common to several fungi form these complex. Thus, elucidation of the primary structure of fungal monohexosylceramides (CMHs) that functions as virulence determinant is important for understanding the mechanism of fungal pathogenicity. In this study, we report on the characterization of glucosylceramides in L. prolificans and the involvement of this molecule on the immune response.