title: Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils.
abstract: In the present study, we characterized the in vitro modulation of NETs (neutrophil extracellular traps) induced in human neutrophils by the opportunistic fungus Cryptococcus neoformans, evaluating the participation of capsular polysaccharides glucuronoxylomanan (GXM) and glucuronoxylomannogalactan (GXMGal) in this phenomenon. The mutant acapsular strain CAP67 and the capsular polysaccharide GXMGal induced NET production. In contrast, the wild-type strain and the major polysaccharide GXM did not induce NET release. In addition, C. neoformans and the capsular polysaccharide GXM inhibited PMA-induced NET release. Additionally, we observed that the NET-enriched supernatants induced through CAP67 yeasts showed fungicidal activity on the capsular strain, and neutrophil elastase, myeloperoxidase, collagenase and histones were the key components for the induction of NET fungicidal activity. The signaling pathways associated with NET induction through the CAP67 strain were dependent on reactive oxygen species (ROS) and peptidylarginine deiminase-4 (PAD-4). Neither polysaccharide induced ROS production however both molecules blocked the production of ROS through PMA-activated neutrophils. Taken together, the results demonstrate that C. neoformans and the capsular component GXM inhibit the production of NETs in human neutrophils. This mechanism indicates a potentially new and important modulation factor for this fungal pathogen.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: Juliana D B
authors.initials: JD
authors.lastname: Rocha
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-900, Brazil.
authors.forename: Michelle T C
authors.initials: MT
authors.lastname: Nascimento
authors.affiliation: Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Seropédica, 23890-000, Brazil.
authors.forename: Debora
authors.initials: D
authors.lastname: Decote-Ricardo
authors.affiliation: Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21045-900, Brazil.
authors.forename: Suzana
authors.initials: S
authors.lastname: Côrte-Real
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-900, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: Norton
authors.initials: N
authors.lastname: Heise
authors.affiliation: Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21045-900, Brazil.
authors.forename: Marise P
authors.initials: MP
authors.lastname: Nunes
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: José Osvaldo
authors.initials: JO
authors.lastname: Previato
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendonça-Previato
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-900, Brazil.
authors.forename: Elvira M
authors.initials: EM
authors.lastname: Saraiva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-900, Brazil.
authors.forename: Célio G
authors.initials: CG
authors.lastname: Freire-de-Lima
mesh_terms: D003455:Cryptococcus neoformans / Q000737:chemistry* / Q000472:pathogenicity; D065206:Extracellular Traps; D062610:Fungal Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D005685:Galactans / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D009504:Neutrophils / Q000187:drug effects; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D062610:Fungal Polysaccharides; D005685:Galactans; D011134:Polysaccharides; D017382:Reactive Oxygen Species; C027478:glucuronoxylomannan