Acetate, a metabolic product of Heligmosomoides polygyrus, facilitates intestinal epithelial barrier breakdown in a FFAR2-dependent manner

Schälter F, Frech M, Dürholz K, Lucas S, Sarter-Zaiss K, Lebon L, Esser-von Bieren J, Dubey LK, Vöhringer D, Schett G, Harris NL, Zaiss M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

International Journal For Parasitology Elsevier

DOI: 10.1016/j.ijpara.2022.04.004

Abstract

Approximately 2 billion people worldwide and a significant part of the domestic livestock are infected with soil-transmitted helminths, of which many establish chronic infections causing substantial economic and welfare burdens. Beside intensive research on helminth-triggered mucosal and systemic immune responses, the local mechanism that enables infective larvae to cross the intestinal epithelial barrier and invade mucosal tissue remains poorly addressed. Here, we show that Heligmosomoides polygyrus infective L3s secrete acetate and that acetate potentially facilitates paracellular epithelial tissue invasion by changed epithelial tight junction claudin expression. In vitro, impedance-based real-time epithelial cell line barrier measurements together with ex vivo functional permeability assays in intestinal organoid cultures revealed that acetate decreased intercellular barrier function via the G-protein coupled free fatty acid receptor 2 (FFAR2, GPR43). In vivo validation experiments in FFAR2−/− mice showed lower H. polygyrus burdens, whereas oral acetate-treated C57BL/6 wild type mice showed higher burdens. These data suggest that locally secreted acetate – as a metabolic product of the energy metabolism of H. polygyrus L3s – provides a significant advantage to the parasite in crossing the intestinal epithelial barrier and invading mucosal tissues. This is the first and a rate-limiting step for helminths to establish chronic infections in their hosts and if modulated could have profound consequences for their life cycle.

Authors with CRIS profile

Michael Frech Department of Medicine 3 – Rheumatology and Immunology Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Sébastien Lucas Department of Medicine 3 – Rheumatology and Immunology Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology David Vöhringer Department of Infection Biology Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

École Polytechnique Fédérale de Lausanne (EPFL) CH Switzerland (CH)

How to cite

APA:

Schälter, F., Frech, M., Dürholz, K., Lucas, S., Sarter-Zaiss, K., Lebon, L.,... Zaiss, M. (2022). Acetate, a metabolic product of Heligmosomoides polygyrus, facilitates intestinal epithelial barrier breakdown in a FFAR2-dependent manner. International Journal For Parasitology. https://doi.org/10.1016/j.ijpara.2022.04.004

MLA:

Schälter, Fabian, et al. "Acetate, a metabolic product of Heligmosomoides polygyrus, facilitates intestinal epithelial barrier breakdown in a FFAR2-dependent manner." International Journal For Parasitology (2022).

BibTeX: Download