The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

Mario M Zaiss, Alexis Rapin, Luc Lebon, Lalit Kumar Dubey, Ilaria Mosconi, Kerstin Sarter, Alessandra Piersigilli, Laure Menin, Alan W Walker, Jacques Rougemont, Oonagh Paerewijck, Peter Geldhof, Kathleen D McCoy, Andrew J Macpherson, John Croese, Paul R Giacomin, Alex Loukas, Tobias Junt, Benjamin J Marsland, Nicola L Harris (Corresponding Author)

Research output: Contribution to journalArticlepeer-review

302 Citations (Scopus)
8 Downloads (Pure)

Abstract

Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions.

Original languageEnglish
Pages (from-to)998-1010
Number of pages13
JournalImmunity
Volume43
Issue number5
Early online date27 Oct 2015
DOIs
Publication statusPublished - 17 Nov 2015

Bibliographical note

We thank Manuel Kulagin for technical help, Pierre Bonnaventure for portal vein blood sampling, Francisco Sepulveda for technical assistance in GS-MS acquisition, and Dorothee Hahne (Metabolomics Australia, University of Western Australia) for human samples SCFA isolation, acquisition, and analysis. We also thank Cristina Cartoni (Phenotyping Unit, EPFL) for Milliplex analysis, Jessica Dessimoz and her team from the Histology Core Facility (EPFL), Miguel Garcia and his team from the Flow Cytometry Core Facility (EPFL), and staff from the EPFL CPG animal house for excellent animal care. The computations were partially performed at the Vital-IT Center for high-performance computing of the SIB Swiss Institute of Bioinformatics (http://www.vital-it.ch). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 310948. Funding for A.W.W. and a subset of the 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Fingerprint

Dive into the research topics of 'The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation'. Together they form a unique fingerprint.

Cite this