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.
Highlights
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
The data suggest that the large quantities of p43 secreted by adult parasites during chronic T. muris infection may serve to interfere with the development of IL-13-dependent host protective immunity
Previous work in other helminth systems has demonstrated the potential of parasite-derived molecules in modulating immune responses either directly or indirectly primarily by influencing the initiation of immune responses or generation of regulatory cell populations[24,25,26]
Summary
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. In addition to underpinning the role of interleukin-13 (IL-13)mediated protective immunity to gastrointestinal-dwelling nematode infections,[5,6] the naturally rodent-infecting species, Trichuris muris, has been successfully used as an experimental model of chronic STH helminth infection[7,8]. Depends upon the ability of Trichuris to disrupt effective IL-13-mediated immunity. Understanding how this group of parasites is able to achieve this, is vital to infection control, and potential elimination as current anthelmintic therapy in humans, is rarely completely effective, with T. trichiura often being the most persistent human STH following anthelmintic treatment[9,10]. The presence of p43 homologs in closely related whipworms, such as T. trichiura, is suggestive of common immunomodulatory function
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