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 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.

Fasciola hepatica serine protease inhibitor family (serpins): Purposely crafted for regulating host proteases

“…High levels of serum periostin have been associated with poor prognosis of different liver diseases, including hepatic steatosis, inflammation and fibrosis [ 63 ]. In the fasciolosis context, we previously identified periostin as a molecular marker of parasite-induced liver pathogenesis in sheep [ 64 ] and here we demonstrate that serum periostin levels agree with fluke number, liver pathology and GGT levels indicating its suitability as a measure of liver pathology during chronic liver fluke infections. Although the rFhSrp1/2 vaccine data did not show a significant level of protection, the vaccine performed better than the rFhCLs that have been reported by various groups to be protective against F .…”

Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

“…The effect caused by Fh15 on the dynamic of macrophage populations is consistent with the effect that F. hepatica newly excysted juveniles (NEJs) cause during their migration through the PerC. Immediately after excystment, NEJs cross the intestinal wall and migrate into the PerC for approximately 3 days after infection (32). During this phase, the parasite recruits a large number of immune cells, specifically macrophages, which are alternatively activated (M2-type macrophages) (33, 34).…”

Eosinophils and Macrophages within the Th2-Induced Granuloma: Balancing Killing and Healing in a Tight Space

“…Eosinophil-rich peritoneal cells collected from infected animals or BMD eosinophils from naive/infected animals are used in functional in vitro eosinophil assays. A major caveat here is the presence of peritoneal macrophages, B cells, and T cells in the lavage fluid (136)(137)(138)(139). Even though eosinophils are the predominant cell type in the peritoneal lavage fluid during parasitic infections (140,141), possible confounding effects of other cell types cannot be discounted (17,18).…”