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

• Published in: Nature communications 2019-05, Vol.10 (1), p.2344-11, Article 2344
• Main Authors: Bancroft, Allison J., Levy, Colin W., Jowitt, Thomas A., Hayes, Kelly S., Thompson, Seona, Mckenzie, Edward A., Ball, Matthew D., Dubaissi, Eamon, France, Aidan P., Bellina, Bruno, Sharpe, Catherine, Mironov, Aleksandr, Brown, Sheila L., Cook, Peter C., S. MacDonald, Andrew, Thornton, David J., Grencis, Richard K.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/109; 13/21; 13/51; 14; 14/19; 14/28; 14/32; 14/35; 14/63; 631/326/417/2546; 631/326/417/2547; 631/535; 82/103; 82/58; 82/80; 82/83; Animals; Chronic infection; Cytokines; Expulsion; Extracellular Matrix - metabolism; Helminth Proteins - immunology; Helminth Proteins - metabolism; Homology; Humanities and Social Sciences; Immunogenicity; Infections; Interleukin 13; Interleukin-13 - immunology; Interleukin-13 - metabolism; Interleukin-13 Receptor alpha2 Subunit - metabolism; Intestinal Diseases, Parasitic - immunology; Intestinal Diseases, Parasitic - metabolism; Intestine; Mice; multidisciplinary; Proteins; Proteoglycans; Proteoglycans - metabolism; Science; Science (multidisciplinary); Secretions; Sequence Homology, Amino Acid; Tethering; Tethers; Thrombospondin; Thrombospondin 1 - metabolism; Trichuriasis; Trichuris - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09996-z

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. In the study, the authors identify a protein excreted by the parasite Trichuris muris , p43, which can modulate IL-13 function, a key cytokine involved in host protection. These data suggest that p43 may be a novel therapeutic target for both whipworm infections and IL13 mediated pathologies.