Fasciola hepatica Kunitz Type Molecule Decreases Dendritic Cell Activation and Their Ability to Induce Inflammatory Responses |
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| Authors: | Cristian R Falcón Diana Masih Gerardo Gatti María Cecilia Sanchez Claudia C Motrán Laura Cervi |
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| Institution: | 1. Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, CIQUIBIC-CONICET, Córdoba, Argentina.; 2. Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.; 3. Foundation for the advancement of Medicine, Córdoba, Argentina.; Institut National de la Santé et de la Recherche Médicale U 872, France, |
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| Abstract: | 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. |
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