Liver Cirrhosis Caused by Food-Borne Zoonotic Fasciola gigantica in Cattle in Bangladesh: Pathology and Immunological Orchestra.

BACKGROUND

Fasciolosis is a food-borne parasitic zoonotic disease caused by widespread liver flukes that affect ruminants and humans, and is responsible for non-resolving hepatic damage. Although fasciolosis occurs in both acute and chronic forms, chronic fasciolosis is more common.

OBJECTIVES

This study investigates the pathological changes and immunological cascade in the livers of Fasciola gigantica infected cattle, both at the transcriptional and translational levels.

METHODS

Normal and suspected liver samples from cattle were collected and examined. Affected tissues were subjected to routine histological and immunohistochemical analysis. Transcription factors and interleukins (IL) were measured by sqRT-PCR and ELISA.

RESULTS

In chronic fasciolosis, liver became atrophied, marked with whitish fibrotic patches, calcification and bile duct hyperplasia filled with blackish-brown sandy contents. Histopathological examinations showed massive loss of hepatocytes, fibrous proliferation, and infiltration of mononuclear cells and eosinophils. In addition, a huge deposition of amyloid was noticed in severely affected livers. T-bet (T-box expressed in T cells protein) remained at the basal level, whereas expression of GATA-3 (GATA-binding protein 3) was dramatically increased in severe fasciolosis. Also, there was a noticeable increase in the GATA-3 positive cells, while T-bet positive cells were largely absent, displaying a drift towards Th2 type immune response. In severe infection, mRNAs of IL-4, IL-5, IL-6, IL-10 and IL-13 highly expressed compared to the non-infected control, but the interferon- (INF)-γ expression remained unaltered. Similarly, we detected significant (p < 0.01) elevation of IL-4, IL-5, IL-6 and IL-13 in severely affected liver lysate. To further validate the notion, bovine peripheral blood mononuclear cells (bPBMCs) were treated with F. gigantica-culture milieu (FCM). FCM treatment elevated IL-4, IL-5, IL-6 and IL-13 in a time dependent manner, confirming liver fluke-induced Th2-biased immune response.

CONCLUSION

This study reveals distinct pathology and dysregulation of transcription factors and cytokines profiles in F. gigantica infected cattle.