Significant differences were considered as follows:p< 0.05;p< 0.01;p< 0.001;****p< 0.0001. == Results == == Eosinophils Are Recruited to the Peritoneal Cavity and Liver DuringF. of activation and cell migration. Depletion of eosinophils with an anti-Siglec-F antibody provoked more severe clinical indicators and increased liver damage than control animals which were accompanied by an increase in the production of IL-10 by hepatic and splenic CD4+T cells. In addition, we also report that eosinophils participate in the modulation of humoral immune responses duringF. hepaticainfection, contributing to their degranulation. In conclusion, we demonstrate that eosinophils are beneficial for the host duringF. hepaticainfection, by limiting the production of IL-10 by specific CD4+T cells and favoring eosinophil degranulation induced by specific antibodies. This work contributes to a better understanding of the role of eosinophils in parasitic helminth infections. Keywords:Fasciola hepatica, eosinophils, immunomodulation, antibodies, degranulation, antibody-dependent cell cytotoxicity == Introduction == Fasciola hepatica, a worldwide-distributed liver fluke, is one of the causative brokers of fasciolosis, a zoonotic disease that affects livestock and humans (1). Indeed, the World Health Organization estimates that around 17 million people are infected and 180 million are at risk of contamination, predominantly in South America and Africa (2). In addition, fasciolosis causes huge economical losses due to livestock contamination, of approximately 3 billion dollars per year (1). The life cycle ofF. hepaticais Cefodizime sodium complex as the parasite goes through multiple stages before reaching its adult form and includes an intermediate host, a water snail of theLymnaeagenus, and a definitive host, usually livestock or humans (3). After ingestion of metacercariae by the mammalian host, juvenile flukes penetrate the hosts intestine wall and reach the liver between 4 and 6 days. Eventually, the flukes reach the bile ducts, where they become sexually mature (3).F. hepaticacauses chronic infections due to sophisticated immune modulation strategies that make possible its long-period survival in the host. Indeed, several studies have Cefodizime sodium shown that this parasite induces regulatory dendritic cells (4,5), option activated macrophages (6), and a type 2 modified immune response characterized by an important regulatory T cell (Treg) component (4,7). Eosinophils, granulocytes belonging to the innate immune system, participate mainly in the defense against multicellular parasites and in several Th2-driven immune disorders, such as asthma, atopic dermatitis, and eosinophilic esophagitis (8). The classical functions of eosinophils include mainly degranulation brought on by antibodies in a mechanism known as antibody-dependent cell cytotoxicity (ADCC) (8,9). However, in the last years, novel immunomodulatory functions have been reported such as the regulation of glucose metabolism in the adipose tissue (10), enhancement of plasma cells survival (11), and suppression of Th1 immune responses (12,13). Eosinophils play a pivotal role in fighting against some helminth infections (9), reflected by their dramatic increase in response to IL-5 produced by CD4+type 2 helper T cells (Th2) (14). Although their capacity for killing helminths through ADCCin vitrohas been well exhibited (15,16), their rolein vivoremains controversial. While in some cases eosinophils appear to Rabbit Polyclonal to KNTC2 be beneficial for the host (17) in others their presence is usually redundant (18) or even of apparent benefit for the parasite (19). InF. hepaticainfection, however, the role of eosinophils remains unknown. In this study we characterized eosinophils during experimental contamination withF. hepaticain mice and demonstrate that they contribute to limit liver damage induced by the parasite by reducing the production of IL-10 by CD4+T cells. In addition, our results indicate that eosinophils play a role in specific humoral immunity by inducing the production of more effective antibodies in triggering eosinophil degranulation. Thus, the present study contributes to the elucidation of immunomodulatory mechanisms mediated by eosinophils duringF. hepaticainfection and collaborates with the understanding of their role in helminth infections. == Materials and Methods == == Ethics Statement == Mouse experiments were carried out in accordance with strict guidelines from the National Committee on Animal Research (Comisin Nacional de Experimentacin Animal, CNEA,http://www.cnea.gub.uy/, National Legislation 18.611, Uruguay) according to the Cefodizime sodium international statements on animal use in biomedical research from the Pan American Health Business (PAHO) and World Health.