Altered Protein Expression in the Ileum of Mice Associated with the Development of Chronic Infections with Echinostoma caproni (Trematoda)

Cortés, Alba; Sotillo, Javier; Muñoz-Antolí, Carla; Fried, Bernard; Esteban, J. Guillermo; Toledo, Rafael

doi:10.1371/journal.pntd.0004082

Cited by 17 publications

(23 citation statements)

References 100 publications

(118 reference statements)

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“…Quantitatively, the proteins involved in metabolic processes were the most altered in any of the groups studied. A generalized reduction of ileal cell metabolism has been observed at 2 weeks after E. [21]. The reduction of aerobic metabolism was associated with an increase in the anaerobic use of glucose, through the overexpression of lactate dehydrogenase.…”

Section: Discussionmentioning

confidence: 95%

“…The creatine kinase energy system is itself further regulated by hypoxic signaling and can enhance creatine metabolism during oxygen deprivation to promote tissue healing and homeostasis [72]. Impaired Cr/PCr shuttling may contribute to dysregulated mitochondrial energetics and an increased barrier permeability characteristic of inflamed mucosa ans susceptibility to E. caproni infection [9,21,73].…”

Section: Discussionmentioning

confidence: 99%

“…Downregulation of peroxiredoxin 1 was observed as a consequence of the curation of an E. caproni infection[38]. The reduced production of this enzyme after infection in presence of rIL-25 may play a double role, promoting crypt-cell proliferation but, at the same time, inducing oxidative stress and ROS-mediated programmed cell death to counteract homeostatic dysregulation induced by the infection[21,[59][60].…”

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confidence: 99%

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Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections

Álvarez-Izquierdo

Esteban

Muñoz-Antolí

et al. 2020

Preprint

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Abstract Background: Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been widely employed to investigate the factors determining the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is essential 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.Methods: To study the mechanisms responsible for resistance elicited by IL-25, we analyze the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compare 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.Results: Quantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Forty of those spots validated protein spots were were identified by mass spectrometry corresponding to 24 proteins.Conclusions: The analysis of differentially expressed proteins indicates that maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death are the most affected processes that appears to be related to the resistance to infection. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections

Álvarez-Izquierdo

Esteban

Muñoz-Antolí

et al. 2020

Preprint

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“…upregulation. E. caproni induces severe epithelial damage in mice and several mechanisms for wound healing are activated early after primary and secondary infection [29][30]46]. In the murine gut, wound environment induces rapid changes in resident microbiota such as changes in microbial alpha or beta diversity [47].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses

Álvarez-Izquierdo

Pérez-Crespo

Esteban

et al. 2020

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Interleukin-25 (IL-25) plays a major role in resistance against intestinal helminth infections as initiator of protective Th2 responses. However, recent studies have challenged the contribution of this cytokine in both the polarization of the response towards a Th2 phenotype and the parasite rejection. We have used the experimental model Echinostoma caproni-ICR mice to investigate the participation of this cytokine in resistance to intestinal helminths. ICR mice are characterized by their inability to respond with IL-25 production in primary infections with E. caproni, causing susceptibility associated with a Th1 response. However, mice are refractory to infection in presence of IL-25 in relation to a type 2 phenotype. Herein, we show that dynamics of resident microbiota appears to be crucial in IL-25 production. Moreover, IL-25 seems to play a pivotal role in the polarization to Th2 in primary responses, but also appears to participate in the generation of memory mechanisms making unnecessary the participation of IL-25 in memory responses for the development of Th2 milieu. However, resistance to E. caproni infection does not depend on the generation of a Th2 phenotype, but exclusively depends on the presence of IL-25, operating autonomously from the type 2 response in the generation of resistance.

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“…These evidences show that GANAB and P4HB are relevant proteins not only in our 12 interactomes, but also in other host-pathogen systems, which confirm these proteins as possible hallmarks of the host-parasite interaction. Other host proteins common in several parasite interactomes ( Fig 7) such as HYOU1, PDIA3, HSPA9, CTSS, etc., have been already found deregulated upon pathogenic infection [78][79][80][81][82][83].…”

Section: Common Targeted Host Proteins Across Interactomesmentioning

confidence: 99%

An integrative method to unravel the host-parasite interactome: an orthology-based approach

Cuesta-Astroz

Santos

Oliveira

et al. 2017

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The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require clear understanding of the molecular crosstalk between parasites and their hosts. As yet, experimental large-scale identification of host-parasite molecular interactions remains challenging and the use of in silico predictions becomes then necessary. Here, we propose a computational integrative approach to predict host-parasite protein-protein interaction (PPI) networks resulting from the infection of human by 12 different parasites. We used an orthology-based method to transfer high-confidence intraspecies interactions obtained from the STRING database to the corresponding inter-species protein pairs in the host-parasite system. To reduce the number of spurious predictions, our approach uses either the parasites predicted secretome and membrane proteins or only the secretome depending on whether they are uni-or multicellular respectively. Besides, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasites growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association to known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. The predicted PPI networks can be visualized and downloaded at http://orthohpi.jensenlab.org. Author SummaryA protein-protein interaction (PPI) network is a collection of interactions between proteins from one or more organisms. Host-parasite PPIs are key to understanding the biology of different parasitic diseases, since predicting PPIs enable to know more about the parasite invasion, infection and persist. Our understanding of PPIs between host and parasites is still . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/147868 doi: bioRxiv preprint first posted online 3 very limited, as no many systematic experimental studies have so far been performed.Efficacy of treatments for parasitic diseases is limited and in many cases parasites evolve resistance. Thus, there is an urgent need to develop novel drugs or vaccines for these neglected diseases, and thus interest in the functions and interactions of proteins associated with parasitism processes. Here we developed an in silico method to shed light on the interactome in twelve human parasites by combining an orthology based strategy and integrating, domain-domain interaction data, sub-cellular localization and to give a spatial context, we only took in to account those human tissues that support the parasite´s tropism.Here we show that is possible to identify relevant interactions across different parasites and their human h...

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Altered Protein Expression in the Ileum of Mice Associated with the Development of Chronic Infections with Echinostoma caproni (Trematoda)

Cited by 17 publications

References 100 publications

Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections

Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections

Interleukin-25-mediated resistance against intestinal trematodes does not depend on the generation of Th2 responses

An integrative method to unravel the host-parasite interactome: an orthology-based approach

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