RESUMO
In this study, we analyzed the impact of immunization with the peptidorhamnomannan (PRM) from the cell wall of the fungus Scedosporium (Lomentospora) prolificans in a murine model of invasive scedosporiosis. Immunization with PRM decreased the survival of mice infected with S. prolificans. Immunization of mice with PRM led to decreased secretion of pro-inflammatory cytokines and chemokines but did not affect the secretion of IL-10. Mice immunized with PRM showed an increase in IgG1 secretion, which is an immunoglobulin linked to a nonprotective response. Splenocytes isolated from mice infected with S. prolificans and immunized with PRM showed no differences in the percentages of Th17 cells and no increase in the frequency of the CD4(+)CD62L(Low) T cell population. PRM-immunized mice showed a significant increase in the percentage of Treg cells. In summary, our results indicated that immunization with PRM did not assist or improve the immunological response against S. prolificans infection. PRM exacerbated the infection process by reducing the inflammatory response, thereby facilitating colonization, virulence and dissemination by the fungus.
Assuntos
Glicoproteínas/metabolismo , Imunossupressores/metabolismo , Micoses/microbiologia , Micoses/patologia , Scedosporium/crescimento & desenvolvimento , Scedosporium/imunologia , Animais , Modelos Animais de Doenças , Feminino , Vacinas Fúngicas/administração & dosagem , Vacinas Fúngicas/imunologia , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologiaRESUMO
Pseudallescheria boydii is an opportunistic fungus widespread in the environment, and has recently emerged as an agent of localized as well as disseminated infections in both immunocompromised and immunocompetent hosts. The host response to fungi is in part dependent on the activation of evolutionary conserved receptors including Toll-like receptors and phagocytic receptors. This review will discuss the isolation and structural characterization of α-glucans and rhamnomannans from P. boydii cell wall and their roles in the induction of innate immune response.
Assuntos
Glucanos/metabolismo , Mananas/metabolismo , Pseudallescheria/química , Scedosporium/química , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Parede Celular/química , Parede Celular/imunologia , Glucanos/química , Glucanos/isolamento & purificação , Humanos , Imunidade Inata , Macrófagos/imunologia , Macrófagos/metabolismo , Mananas/química , Mananas/isolamento & purificação , Monócitos/imunologia , Monócitos/metabolismo , Micoses/imunologia , Micoses/microbiologia , Pseudallescheria/imunologia , Scedosporium/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologiaRESUMO
Isolated from the mycelium of Scedosporium prolificans were complex glycoproteins (RMP-Sp), with three structurally related components (HPSEC). RMP-Sp contained 35% protein and 62% carbohydrate with Rha, Ara, Man, Gal, Glc, and GlcNH(2) in a 18:1:24:8:6:5 molar ratio. Methylation analysis showed mainly nonreducing end- of Galp (13%), nonreducing end- (9%), 2-O- (13%), and 3-O-subst. Rhap (7%), nonreducing end- (11%), 2-O- (10%), 3-O- (14%), and 2,6-di-O-subst. Manp units (13%). Mild reductive beta-elimination of RMP-Sp gave alpha-l-Rhap-(1-->2)-alpha-l-Rhap-(1-->3)-alpha-l-Rhap-(1-->3)-alpha-d-Manp-(1-->2)-d-Man-ol, with Man-ol substituted at O-6 with beta-d-Galp units, a related pentasaccharide lacking beta-d-Galp units, and beta-d-Galp-(1-->6)-[alpha-d-Manp-(1-->2)]-d-Man-ol in a 16:3:1w/w ratio. Traces of Man-ol and Rha-ol were detected. ESI-MS showed HexHex-ol and Hex(3-6)Hex-ol components. Three rhamnosyl units were peeled off successively from the penta- and hexasaccharide by ESI-MS-MS. The carbohydrate epitopes of RMP-Sp differ from those of the glycoprotein of Pseudallescheria boydii, a related opportunistic pathogen.