Study of the cross-talk between Fasciola hepatica juveniles and the intestinal epithelial cells of the host by transcriptomics in an in vitro model

9 páginas, 5 figuras

Fasciolosis is a globally widespread trematodiasis with a major economic and veterinary impact. Therefore, this disease is responsible for millions of dollars in losses to the livestock industry, and also constitutes an emerging human health problem in endemic areas. The ubiquitous nature of Fasciola hepatica, the main causative agent, is one of the key factors for the success of fasciolosis. Accordingly, this parasite is able to subsist in a wide variety of ecosystems and hosts, thanks to the development of a plethora of strategies for adaption and immune evasion. Fasciolosis comprises a growing concern due to its high prevalence rates, together with the emergence of strains of the parasite resistant to the treatment of choice (triclabendazole). These facts highlight the importance of developing novel control measures which allow for an effective protection against the disease before F. hepatica settles in a niche inaccessible to the immune system. However, knowledge about the initial phases of the infection, including the migration mechanisms of the parasite and the early innate host response, is still scarce. Recently, our group developed an in vitro host-parasite interaction model that allowed the early events to be unveiled after the first contact between the both actors. This occurs shortly upon ingestion of F. hepatica metacercariae and the emergence of the newly excysted juveniles (FhNEJ) in the host duodenum. Here, we present a transcriptomic analysis of such model using an approach based on RNA sequencing (RNA-Seq), which reveals changes in gene expression related to proteolysis and uptake of metabolites in FhNEJ. Additionally, contact with the parasite triggered changes in host intestinal cells related to pseudogenes expression and host defence mechanisms, including immune response, among others. In sum, these results provide a better understanding of the early stages of fasciolosis at molecular level, and a pool of targets that could be used in future therapeutic strategies against the disease.

M.S.L. acknowledges the financial support of the Spanish Ministry of Science and Innovation (grant numbers AGL2015-67023-C2-2-R and PID2019-108782RB-C22) and the Junta de Castilla y Leon ´ “IRNASA/ CSIC Unit of Excellence” co-financed by the European Union (ERDF “Europe drives our growth”) (grant number CLU-2019-05). D.B.R. and J. S. acknowledge the support of the Junta de Castilla y León for their Predoctoral contracts. M.L.G. acknowledges the support of the Spanish Ministry of Science and Innovation for her FPU Predoctoral contract. J. G.M. is supported by the ‘Ramón y Cajal’ program of the Spanish Ministerio de Ciencia e Innovación (grant number RYC2020-030575-I). M.T. V. acknowledges the support of the European Commission NextGenerationEU Fund (grant number EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global)

Peer reviewed