Early and Late Peritoneal and Hepatic Changes in Goats Immunized with Recombinant Cathepsin L1 and Infected with Fasciola hepatica

Zafra, R.; Pérez-Écija, Alejandro; Buffoni, L.; Moreno, P.; Bautista, M.J.; Martı́nez-Moreno, A.; Mulcahy, Grace; Dalton, John P.; Pérez, J.

doi:10.1016/j.jcpa.2012.08.007

Cited by 35 publications

(39 citation statements)

References 42 publications

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“…Most notable was the very marked eosinophilia (49% of immune cells). Eosinophilia is also observed within the peritoneum during the early stages of infection in rats 37 , and was observed by both histocytochemical studies 22, 23, 38 and transcriptome analysis of F. hepatica -infected sheep liver 39, 40 . Marked eosinophilia is typical of helminth infections that drive Th2-dominant immune responses and in some cases, for example primary filarial infections 41 and schistosomiasis 42, 43 , is associated with significant immune protection.…”

Section: Discussionmentioning

confidence: 89%

“…22, 23 . The recovered peritoneal fluid was centrifuged at 430 × g for 5 min and the supernatant and cell pellet retained.…”

Section: Methodsmentioning

confidence: 99%

“…Studies have shown that as the parasite migrates through the intestinal epithelium clinical signs are not evident, although an immunological response is induced, as illustrated by the large number of immune cells infiltrating into the peritoneal cavity 22, 23 . Since the parasite migrates from the intestine to the liver via the peritoneum we considered that investigation of the peritoneal compartment of infected animals may provide new information of the early immune response in this compartment that can be exploited for vaccine development.…”

Section: Introductionmentioning

confidence: 99%

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Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Ruiz-Campillo

Molina-Hernández

Escamilla

et al. 2017

Sci Rep

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Immune signatures of sheep acutely-infected with Fasciola hepatica, an important pathogen of livestock and humans were analysed within the peritoneal compartment to investigate early infection. Within the peritoneum, F. hepatica antibodies coincided with an intense innate and adaptive cellular immune response, with infiltrating leukocytes and a marked eosinophilia (49%). However, while cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated, these were not statistically different at 18 days post-infection compared to uninfected animals indicating that the immune response is muted and not yet skewed to a Th2 type response that is associated with chronic disease. Proteomic analysis of the peritoneal fluid identified infection-related proteins, including several structural proteins derived from the liver extracellular matrix, connective tissue and epithelium, and proteins related to the immune system. Periostin and vascular cell adhesion protein 1 (VCAM-1), molecules that mediate leukocyte infiltration and are associated with inflammatory disorders involving marked eosinophilia (e.g. asthma), were particularly elevated in the peritoneum. Immuno-histochemical studies indicated that the source of periostin and VCAM-1 was the inflamed sheep liver tissue. This study has revealed previously unknown aspects of the immunology and pathogenesis associated with acute fascioliasis in the peritoneum and liver.

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Section: Discussionmentioning

confidence: 89%

“…22, 23 . The recovered peritoneal fluid was centrifuged at 430 × g for 5 min and the supernatant and cell pellet retained.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Ruiz-Campillo

Molina-Hernández

Escamilla

et al. 2017

Sci Rep

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“…In cattle and sheep, F. hepatica induces a liver and blood eosinophilia and F. gigantica infection of sheep gives the same profile (Chauvin, Moreau, & Boulard, ; Zhang et al., ). Paradoxically under the cover of vaccination calves and goats showing protection had reduced eosinophil counts (Wedrychowicz et al., ; Zafra, Pérez‐Écija, Buffoni, Moreno et al., ). This is further complicated by findings using Indonesian thin tailed (ITT) sheep who display resistance to F. gigantica but not F. hepatica .…”

Section: Immunity To Fasciola Sppmentioning

confidence: 99%

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

Beesley

Caminade

Charlier

et al. 2017

Transbound Emerg Dis

146

111

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Summary Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re‐emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune‐modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.

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“…F. hepatica cathepsin B is mainly expressed in metacercariae and newly excysted juveniles whilst cathepsin L is mainly expressed in newly excysted juveniles and adult worms [45]. F. hepatica cathepsins are considered important vaccine candidates; several studies have demonstrated their protection-inducing ability in different experimental models [46–49]. F. hepatica amoebapore proteins have shown amino acid sequence similarity with saposin-like proteins.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model

et al. 2017

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BackgroundFasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica.MethodsThe mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks.ResultsMice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value <0.05, fold change ranging from −2.944 to 7.632. A functional study of these genes revealed changes in the pathways related to nitric oxide and reactive oxygen species production, Interleukin-12 signalling and production in macrophages and Interleukin-8 signalling with up-regulation of S100 calcium-binding protein A8, Matrix metallopeptidase 9 and CXC chemokine receptor 2 genes.ConclusionThe data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against F. hepatica in a murine model, which could be useful for evaluating future vaccine candidates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2205-3) contains supplementary material, which is available to authorized users.

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Early and Late Peritoneal and Hepatic Changes in Goats Immunized with Recombinant Cathepsin L1 and Infected with Fasciola hepatica

Cited by 35 publications

References 42 publications

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model

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