Falcón Cristian R, Masih Diana, Gatti Gerardo, Sanchez María Cecilia, Motrán Claudia C, Cervi Laura
Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, CIQUIBIC-CONICET, Córdoba, Argentina.
Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.
PLoS One. 2014 Dec 8;9(12):e114505. doi: 10.1371/journal.pone.0114505. eCollection 2014.
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.
肝片吸虫（Fh）中具有免疫调节活性的蛋白质完整库尚未得到充分描述。在此，我们证明Fh总提取物（TE）可降低LPS诱导的树突状细胞（DC）成熟以及DC诱导同种异体反应的能力。对TE进行分级分离后，低于10 kDa的级分（F<10 kDa）能够保持TE调节LPS诱导的DC促炎和抗炎细胞因子产生的特性。此外，TE或F<10 kDa处理降低了未成熟DC刺激同种异体反应的能力，并诱导了新的同种异体CD4+CD25+Foxp3+ T细胞。相反，用T/L或F<10 kDa加LPS（F<10/L）处理DC会诱导一种依赖IL-27的调节机制，该机制会减弱增殖以及Th1和Th17同种异体反应。最后，我们表明存在于F<10 kDa中的一种Kunitz型分子（Fh-KTM）通过在DC上赋予耐受原性特征来抑制LPS激活的DC中促炎细胞因子的产生，从而损害其诱导炎症反应的能力。这些结果表明该蛋白具有调节作用，可能参与了寄生虫的免疫逃避机制。
