Resumo

We characterized the production in vitro of human NETs (neutrophil extracellular traps) induced by the opportunistic fungus Cryptococcus neoformans, evaluating participation of purified capsular polysaccharides Glucuronoxylomannan (GXM) and Galactoxylomannan (GalXM) in this phenomenon. The strain CAP67 (mutant non-capsulated) and the purified capsular polysaccharide GalXM were capable of inducing the production NETs. In contrast, we observed that wild-type encapsulate strain and the purified polysaccharide GXM were not capable of inducing the release of NETs. We described that wild-type Cryptococcus neoformans and the capsular component GXM inhibited NETs production by PMA. In parallel, we found that the NETs induced by the fungus mutant non-capsulated CAP67 had microbicidal action on the wild-type encapsulate strain and that the neutrophil elastase, myeloperoxidase, collagenase and histone were key killing components of NETs. We investigated the signaling pathways associated with the NETs induction, focusing on the role of reactive oxygen species (ROS), we concluded that both strains were able to induce the production of ROS. Finally we evaluated whether the capsular polysaccharides GXM and GalXM modulate signaling pathways that lead to the production of ROS by neutrophils; and we observed that alone, both purified capsular polysaccharides glucuronoxylomannan (GXM) and galactoxylomannan (GalXM) do not induced the production of ROS; however in neutrophils activated with PMA, both purified capsular polysaccharides were capable of inhibiting ROS production. Therefore we described that the Cryptococcus neoformans and its capsular polysaccharide GXM inhibited NETs production by human neutrophils, and this processes could be considered a description of a new virulence mechanism of this pathogen.