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

ABSTRACT: 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 TGF? 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.

SUBMITTER: Ruiz-Campillo MT

PROVIDER: S-EPMC5459796 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Ruiz-Campillo Maria Teresa MT Molina Hernandez Veronica V Escamilla Alejandro A Stevenson Michael M Perez Jose J Martinez-Moreno Alvaro A Donnelly Sheila S Dalton John P JP Cwiklinski Krystyna K

Scientific reports 20170605 1

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 ...[more]

PMID: 28584245

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Project description:The liver fluke Fasciola hepatica is an economically important pathogen of livestock. Fasciolosis in humans is an important re-emerging zoonosis, with 180 million people at risk. Development of novel control strategies requires an understanding of parasite virulence and tissue invasion, and of how the parasite evades and modulates the immune response during early infection. A combination of immunological and proteomic analyses was employed to investigate the peritoneal fluid of sheep infected with F. hepatica to characterise early tissue invasion and liver pathogenesis. At 18 days post-infection (dpi), histopathology of sheep liver showed white necrotic foci/tracts indicative of F. hepatica migration. Within the peritoneal fluid of infected animals, specific F. hepatica antigen FhCL1 antibodies coincided with an intense innate and adaptive cellular immune response, with increasing numbers of total leukocytes and a marked eosinophilia (49%). Cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated but not statistically significant at 18 dpi compared to uninfected sheep indicating that whilst the immune response is developing it has not polarised to the Th2 type associated with chronic fasciolosis. Proteomic analysis of the peritoneal fluid identified 178 proteins, with 25 proteins more highly expressed in the infected animals, based on fold changes in protein concentration compared to the uninfected animals. Components of the liver extracellular matrix, including collagen, periostin and the adhesion protein, VCAM-1, exhibited increased expression associated with early fasciolosis, which may be important in signalling host immune responses to tissue damage. In early F. hepatica infection cellular infiltration with marked eosinophilia, adaptive immune responses and products of liver pathology are evident in the peritoneum. Although cytokine responses are developing they are mixed and not yet polarised to a Th2-type. We have characterised biomarkers of parasite-induced liver damage which could be exploited for diagnosis, and vaccine development aimed at reducing/preventing liver pathology.

Dataset Information

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

Publications

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

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