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

Maria Teresa Ruiz-Campillo,Jose Perez,Sheila Donnelly,Alvaro Martinez-Moreno,Michael Stevenson,Veronica Molina Hernandez,John P. Dalton,Krystyna Cwiklinski,Alejandro Escamilla

doi:10.1038/s41598-017-03094-0

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 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.

Highlights

Fasciolosis is a disease of ruminants caused by the liver fluke Fasciola hepatica, and results in worldwide economic losses of greater than US $3 billion per annum[1,2,3]
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
Portal spaces adjacent to necrotic foci showed severe inflammatory infiltrate suggesting that the route of the infiltrating inflammatory cells was through the portal vessels

Summary

Introduction

Fasciolosis is a disease of ruminants caused by the liver fluke Fasciola hepatica, and results in worldwide economic losses of greater than US $3 billion per annum[1,2,3] It is recognised by the World Health Organisation (WHO) as an important zoonosis; global infections are estimated between 2 and 17 million, with 180 million people at risk of infection[4,5,6]. The NEJs traverse the intestinal wall into the peritoneal cavity, where they continue to migrate through the liver capsule into the liver parenchyma Those parasites that reach the liver, normally between four and six days post-infection, cause extensive tissue damage and haemorrhaging in the liver parenchyma resulting in the hepatic pathogenesis associated with acute fasciolosis[12]. The data could identify important host-specific proteins related to infection

Methods

Results

Conclusion