A host-independent role for Fasciola hepatica transforming growth factor-like molecule in parasite development. Issue 6 (May 2021)

• Record Type: Journal Article
• Authors: Musah-Eroje, Mayowa; Hoyle, Rebecca C.; Japa, Ornampai; Hodgkinson, Jane E.; Haig, David M.; Flynn, Robin J.
• Is Part Of: International journal for parasitology. Volume 51:Issue 6(2021)
• Page Start: 481
• Page End: 492
• Publication Date: 2021-05
• Subjects: Fasciola hepatica -- TGF homologue -- Helminth -- Immunomodulation; Parasitology -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; Parasitology; Periodicals; Electronic journals; 571.999
• DOI: 10.1016/j.ijpara.2020.11.005
• Languages: English
• ISSNs: 0020-7519

Abstract

Graphical abstract: Highlights: Fasciola hepatica TGF-like molecule ( Fh TLM) fails to provoke Foxp3 + CD4 T-cells. CD4 T-cells exposed to Fh TLM display heightened chemokine secretion. Fh TLM-elicited granulocytes do not promote parasite development. Abstract: The trematode parasite Fasciola hepatica causes chronic infection in hosts, enabled by an immunosuppressed environment. Both host and parasite factors are known to contribute to this suggesting that avoidance of immunopathology is beneficial to both parties. We have previously characterised a parasite transforming growth factor (TGF)-like molecule, FhTLM, that interacts with host macrophages to prevent antibody-dependent cell cytotoxicity (ADCC). FhTLM is one of many described helminth TGF homologues and multiple helminths are now known to utilise host immune responses as developmental cues. To test whether, or how, F. hepatica uses FhTLM to manipulate host immunity, we initially examined its effects on the CD4 T-cell phenotype. Despite inducing IL-10, there was no induction of FoxP3 within the CD4 T-cell compartment. In addition to inducing IL-10, a wide range of chemokines were elicited from both CD4 T-cells and macrophages. However, no growth or survival advantage was conferred on F. hepatica in our co-culture system when CD4 T-cells, macrophages, or eosinophils were tested. Finally, using RNA interference we were able to verify a host-independent role for FhTLM in parasite growth. Despite the similarities of FhTLM with other described helminth TGF homologues, here we demonstrate species-specific divergence.