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Nat Commun. 2019 May 28;10(1):2344. doi: 10.1038/s41467-019-09996-z.

The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function.

Bancroft AJ1,2,3,4, Levy CW5, Jowitt TA6,7, Hayes KS8,6,9,7, Thompson S8,6,9,7, Mckenzie EA5, Ball MD5, Dubaissi E8,6,9,7, France AP5, Bellina B5, Sharpe C8,6,9,7, Mironov A7, Brown SL8,9,7,10, Cook PC8,9,7,10, S MacDonald A8,9,7,10, Thornton DJ8,6,9,7, Grencis RK11,12,13,14.

Author information

1
Lydia Becker Institute for Immunology and Inflammation, Manchester, M13 9PT, UK. allison.j.bancroft@manchester.ac.uk.
2
Wellcome Trust Centre for Cell Matrix Research, Manchester, M13 9PT, UK. allison.j.bancroft@manchester.ac.uk.
3
Division of Infection, Immunity and Respiratory Medicine, Manchester, M13 9PT, UK. allison.j.bancroft@manchester.ac.uk.
4
School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK. allison.j.bancroft@manchester.ac.uk.
5
Manchester Institute of Biotechnology, University of Manchester, 3.020 Garside Building, 131 Princess Street, Manchester, M1 7DN, UK.
6
Wellcome Trust Centre for Cell Matrix Research, Manchester, M13 9PT, UK.
7
School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK.
8
Lydia Becker Institute for Immunology and Inflammation, Manchester, M13 9PT, UK.
9
Division of Infection, Immunity and Respiratory Medicine, Manchester, M13 9PT, UK.
10
Manchester Collaborative Centre for Inflammation Research, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Core Technology, University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
11
Lydia Becker Institute for Immunology and Inflammation, Manchester, M13 9PT, UK. Richard.Grencis@manchester.ac.uk.
12
Wellcome Trust Centre for Cell Matrix Research, Manchester, M13 9PT, UK. Richard.Grencis@manchester.ac.uk.
13
Division of Infection, Immunity and Respiratory Medicine, Manchester, M13 9PT, UK. Richard.Grencis@manchester.ac.uk.
14
School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK. Richard.Grencis@manchester.ac.uk.

Abstract

Infection by soil transmitted parasitic helminths, such as Trichuris spp, are ubiquitous in humans and animals but the mechanisms determining persistence of chronic infections are poorly understood. Here we show that p43, the single most abundant protein in T. muris excretions/secretions, is non-immunogenic during infection and has an unusual sequence and structure containing subdomain homology to thrombospondin type 1 and interleukin (IL)-13 receptor (R) α2. Binding of p43 to IL-13, the key effector cytokine responsible for T. muris expulsion, inhibits IL-13 function both in vitro and in vivo. Tethering of p43 to matrix proteoglycans presents a bound source of p43 to facilitate interaction with IL-13, which may underpin chronic intestinal infection. Our results suggest that exploiting the biology of p43 may open up new approaches to modulating IL-13 function and control of Trichuris infections.

PMID:
31138806
PMCID:
PMC6538607
DOI:
10.1038/s41467-019-09996-z
[Indexed for MEDLINE]
Free PMC Article

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