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

Abstract

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)-&#x3b3; expression remained unaltered. Similarly, we detected significant (p&#x2009;<&#x2009;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.