Abstract
BackgroundEchinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been extensively used to investigate the factors that determine the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is critical for the development of resistance against E. caproni in mice. In fact, treatment of mice with recombinant IL-25 generates resistance against primary E. caproni infection. However, the mechanisms by which IL-25 induces resistance remain unknown.MethodsTo study the mechanisms responsible for resistance elicited by IL-25, we analyzed the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compared the protein expression profiles in the ileum of four experimental groups of mice: naïve controls; E. caproni-infected mice; rIL-25-treated mice; and rIL-25-treated mice exposed to E. caproni metacercariae.ResultsQuantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Of these, 40 validated protein spots were identified by mass spectrometry corresponding to 24 proteins.ConclusionsOur results indicate that resistance to infection is associated with the maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.
Highlights
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been exten‐ sively used to investigate the factors that determine the rejection of intestinal helminths
Analysis of protein production profiles by 2D‐DIGE The 2D-DIGE proteomic analysis was implemented on whole ileal cell extracts in a total of 12 replicates, corresponding to 4 experimental groups (3 replicates each) referred as: control, rIL-25-treated mice; rIL-25treated mice exposed to metacercariae; and infected mice. 2D-images were analyzed using the DeCyder software and both multivariate and univariate analysis were applied to identify: (i) the similarity in intestinal protein production profiles among experimental groups; and (ii) particular differences in protein abundance between each group with respect to the others (Additional file 1: Figure S1, Additional file 2: Figure S2, Additional file 3: Figure S3)
Following the results of the multivariate statistical analyses, the 4 experimental groups were used as 3 comparative pairs due to their importance to analyze the role of IL-25: (i) infected animals vs rIL-25-treated animals; (ii) rIL-25-treated mice exposed to metacercariae vs rIL-25-treated animals; and (iii) naïve controls vs rIL-25-treated mice (Figs. 1, 2, 3)
Summary
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been exten‐ sively used to investigate the factors that determine the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is critical for the development of resistance against E. caproni in mice. Intestinal helminth infections affect more than one billion people worldwide, mainly in developing regions of Asia, Africa and Latin America [1] These infections cause high morbidity, with most common symptoms related to effects on nutrition inducing malabsorption syndrome, vitamin deficiencies, growth retardation or impaired cognitive function among other disorders. The infection becomes chronic, while in hosts of low compatibility, such as rats, the worms are rapidly rejected in a few weeks post-infection (wpi) [8, 9]
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