Fasciola hepatica Kunitz type molecule decreases dendritic cell activation and their ability to induce inflammatory responses

FALCON CR; MASIH DT; GATTI G; SANCHEZ MC; MOTRAN CC; CERVI L

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 8

1932-6203

The complete repertoire of proteins with immunomodulatory activity in Fasciola hepatica (Fh) has not yet been fully described. Here, we demonstrated that Fh total extract (TE) reduced LPS-induced DC maturation, and the DC ability to induce allogeneic 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- and anti-inflammatory cytokine production induced by LPS. In addition, TE or F ,10 kDa treatment decreased the ability of immature DC to stimulate the allogeneic responses 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 Th17 allogeneic responses. Finally, we showed that a Kunitz type molecule (Fh-KTM), present in F ,10 kDa, was responsible for suppressing pro-inflammatory cytokine production in LPS-activated DC, by printing tolerogenic features on DC that impaired their ability to induce inflammatory responses. These results suggest a modulatory role for this protein, which may be involved in the immune evasion mechanisms of the parasite. OPEN ACCESS Citation: Falco´n CR, Masih D, Gatti G, Sanchez MC, Motra´n CC, et al. (2014) Fasciola hepatica Kunitz Type Molecule Decreases Dendritic Cell Activation and Their Ability to Induce Inflammatory Responses. PLoS ONE 9(12): e114505. doi:10. 1371/journal.pone.0114505 Editor: Jagadeesh Bayry, Institut National de la Sante´ et de la Recherche Me´dicale U 872, France Received: May 22, 2014 Accepted: November 10, 2014 Published: December 8, 2014 Copyright: 2014 Falco´n et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper