Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes

Abstract

BackgroundDetermining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection.MethodsWater buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-β, IL-1β, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology.ResultsHistopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3–10 dpi) was marked by a generalized immunosuppression and elevated TGF-β expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host’s Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis.ConclusionsOur data showed distinct CD4+ T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity.

Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro

“…In the course of our previous research, a modest Th2 response at the early stage of infection was found to balance harmful Th1 and Th17 responses in F. gigantica -infected buffaloes [ 46 ]. We also observed that F. gigantica infection had a significant impact on the expression of Th1, Th2, Th17, and Treg cytokines [ 47 ]. IL-17 is important in the host defense against extracellular pathogens, predominantly at mucosal sites.…”

Fasciolosis: grading the histopathological lesions in naturally infected bovine liver in Mosul city

“…The affected cells will increase the releasing of IL-13 that act as a trigger to T-helper 2 lymphocytes to overcome the continuous irritation (20). With time the lesions caused by Fasciola spp were increased in severity, this occurs due to increase in the level of tumor growth factor -beta (TGF-β) which cause immunosuppression of host defenses to facilitate parasite colonization (21).…”

A recombinant Fasciola gigantica 14-3-3 epsilon protein (rFg14-3-3e) modulates various functions of goat peripheral blood mononuclear cells

“…Our observation that rFg14-3-3e protein suppresses immune response is in line with what we described previously during F. gigantica infection in buffaloes. An ‘early’ TGF-β-associated immuno-suppressive response together with upregulation of liver IL-10 mRNA expression [ 52 ] and increased level of serum IL-10 cytokine [ 53 ] have been observed in buffaloes during early F. gigantica infection. In another study, we reported downregulation of MHC-II related genes and suppression of the host pro-inflammatory (Th1) immune response during early F. gigantica infection in buffalo liver [ 54 ].…”