Fasciola hepatica Kunitz Type Molecule Decreases Dendritic Cell Activation and Their Ability to Induce Inflammatory Responses

FALCÓN CRISTIAN ROBERTO; MASIH DIANA; GATTI GERARDO; SANCHEZ MARÍA CECILIA; MOTRÁN CRISTINA; CERVI LAURA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014

1932-6203

The complete repertoire of proteins with immunomodulatory activity in Fasciolahepatica (Fh) has not yet been fully described. Here, we demonstrated that Fh totalextract (TE) reduced LPS-induced DC maturation, and the DC ability to induceallogeneic responses. After TE fractionating, a fraction lower than 10 kDa(F,10 kDa) was able to maintain the TE properties to modulate the DC pro- andanti-inflammatory cytokine production induced by LPS. In addition, TE or F,10 kDatreatment decreased the ability of immature DC to stimulate the allogeneicresponses and induced a novo allogeneic CD4+CD25+Foxp3+ T cells. In contrast,treatment of DC with T/L or F,10 kDa plus LPS (F,10/L) induced a regulatory IL-27 dependent mechanism that diminished the proliferative and Th1 and Th17allogeneic responses. Finally, we showed that a Kunitz type molecule (Fh-KTM),present in F,10 kDa, was responsible for suppressing pro-inflammatory cytokineproduction in LPS-activated DC, by printing tolerogenic features on DC thatimpaired their ability to induce inflammatory responses. These results suggest amodulatory role for this protein, which may be involved in the immune evasionmechanisms of the parasite.