Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells

RODRIGUEZ ERNESTO; NOYA V; . CERVI L.; CHIRIBAO MARIA LAURA; BROSSARD NATALIE; CAROLINA CHIALE; CARLOS CARMONA; GIACOMINI CECILIA; TERESA FREIRE

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 vol. 31 p. 1 - 26

1935-2735

AbstractHelminthsexpressvariouscarbohydrate-containingglycoconjugatesontheirsurface, and theyreleaseglycan-richexcretion/secretion productsthatcanbeveryimportantintheirlife cycles,infectionandpathology.Recentevidencesuggeststhatparasiteglycoconjugates couldplayaroleintheevasionoftheimmuneresponse,leadingtoamodifiedTh2-polarizedimmuneresponsethatfavorsparasite survival inthehost.Nevertheless,thereislimitedinformationaboutthenatureorfunctionofglycansproducedbythetrematodeFasciola hepatica,thecausativeagentoffasciolosis.Inthispaper, weinvestigatewhetherglycosylatedmolecules fromF.hepaticaparticipateinthemodulationofhostimmunity.Wealso focusondendriticcells,sincetheyareanimportanttargetofimmune-modulationbyhelminths, affectingtheiractivityorfunction.OurresultsindicatethatglycansfromF.hepatica promotetheproductionofIL-4andIL-10,suppressingIFNγproduction.Duringinfection, thisparasiteisabletoinduceasemi-maturephenotypeofDCsexpressing lowlevelsof MHCIIandsecreteIL-10.Furthermore,weshowthatparasite glycoconjugatesmediatethe modulationofLPS-induced maturationofDCssincetheiroxidationrestoresthecapacityof LPS-treatedDCstosecretehighlevelsofthepro-inflammatory cytokinesIL-6andIL-12/ 23p40andlowlevelsoftheanti-inflammatorycytokineIL-10.Inhibitionassaysusingcarbohydratessuggestthattheimmune-modulationismediated,atleastinpart,bytherecognitionofamannosespecific-CLRthatsignalsbyrecruitingthephosphatasePhp2.The resultspresentedherecontributetotheunderstandingoftheroleofparasiteglycosylated molecules inthemodulationofthehostimmunityandmightbeusefulinthedesignofvaccinesagainstfasciolosis.