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

Shi, Wei; Wei, Zhi-Yong; Elsheikha, Hany M.; Zhang, Fu-Kai; Sheng, Zhao-An; Lu, Ke-Jing; Wang, Dong-Ying; Huang, Wei-Yi; Zhu, Xing-Quan

Authors

Wei Shi

Zhi-Yong Wei

Hany M. Elsheikha

Fu-Kai Zhang

Zhao-An Sheng

Ke-Jing Lu

Dong-Ying Wang

Wei-Yi Huang

Xing-Quan Zhu



Abstract

Background

Determining 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.
Methods

Water 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.
Results

Histopathological 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.
Conclusions

Our 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.

Journal Article Type Article
Publication Date Dec 8, 2017
Journal Parasites & Vectors
Electronic ISSN 1756-3305
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 602
APA6 Citation Shi, W., Wei, Z., Elsheikha, H. M., Zhang, F., Sheng, Z., Lu, K., …Zhu, X. (2017). Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes. Parasites and Vectors, 10(1), https://doi.org/10.1186/s13071-017-2538-1
DOI https://doi.org/10.1186/s13071-017-2538-1
Keywords Fasciola gigantica; Buffaloes; Liver; Cytokines; Transcription factors; Gene expression
Publisher URL https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-017-2538-1
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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