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Mucosal trapping and degradation of Nippostrongylus brasiliensis occurs in the absence of STAT6

Published online by Cambridge University Press:  27 February 2013

NICHOLAS VAN PANHUYS ,
MALI CAMBERIS ,
MINORU YAMADA ,
TATSUYA TEGOSHI ,
NAOKI ARIZONO  and
GRAHAM LE GROS
NICHOLAS VAN PANHUYS*
Affiliation:
Laboratory of Systems Biology, NIAID, NIH, 9000 Rockville Pike Building 4, Room 128, MSC 0421, Bethesda, MD 20892, USA
MALI CAMBERIS
Affiliation:
Malaghan Institute of Medical Research, Gate 7, Victoria University, Kelburn Pde, PO Box 7060, Wellington 6242, New Zealand
MINORU YAMADA
Affiliation:
Department of Medical Zoology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kyoto 602-0841, Japan
TATSUYA TEGOSHI
Affiliation:
Department of Medical Zoology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kyoto 602-0841, Japan
NAOKI ARIZONO
Affiliation:
Department of Medical Zoology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kyoto 602-0841, Japan
GRAHAM LE GROS
Affiliation:
Malaghan Institute of Medical Research, Gate 7, Victoria University, Kelburn Pde, PO Box 7060, Wellington 6242, New Zealand
*
*Corresponding author: Laboratory of Systems Biology, NIAID, NIH, 9000 Rockville Pike Building 4, Room 128, MSC 0421, Bethesda, MD 20892, USA. Tel: 301-496-3115. Fax: 301-480-7352. E-mail: vanpanhuysn@niaid.nih.gov
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Summary

Hookworms represent a major infectious burden globally, especially in developing countries. The murine hookworm Nippostrongylus brasiliensis is normally cleared in a manner dependent on IL-13, IL4-R and STAT6 signalling. Here we have used STAT6-deficient animals to model a non-resistant population and describe 2 novel STAT6-independent processes for the clearance of N. brasiliensis. During primary infection STAT6−/− animals are able to clear gut-dwelling N. brasiliensis by a mechanism involving the trapping and degradation of worms in the gut mucosa. Here, a previously undescribed STAT6-independent up-regulation of Relm-β was observed which correlated with the mucosal trapping and degradation of worms. Previous studies have indicated that during secondary infection STAT6 deficient animals fail to expel adult worms and remain susceptible to re-infection and long-term colonization of the gut. We report here that an initial partially protective response occurs early upon re-infection in the absence of STAT6, and that a late-phase protective secondary response arises in the gut of STAT6-deficient mice leading to the clearance of the majority of N. brasiliensis, through their trapping and death in the mucosal layer of the lower region of the small intestine. These findings show that there are a number of redundant effector pathways which act to reduce worm burden in the gut which can be activated by mechanisms that do not work through the dominant STAT6 signalling pathway and may be useful as targets for future vaccination strategies against resistant hookworm strains.

Keywords

Nippostrongylus brasiliensisSTAT6TH2mucosal trapping
Type
Research Article
Information
Parasitology , Volume 140 , Issue 7 , June 2013 , pp. 833 - 843
Creative Commons
This is a work of the U.S. Government and is not subject to copyright protection in the United States.
Copyright
Copyright © Cambridge University Press 2013

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