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

Nicholas J. Van Panhuys, Mali Camberis, Minoru Yamada, Tatsuya Tegoshi, Naoki Arizono, Graham Le Gros

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)833-843
Number of pages11
JournalParasitology
Volume140
Issue number7
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Fingerprint

Nippostrongylus
Nippostrongylus brasiliensis
Ancylostomatoidea
trapping
hookworms
digestive system
degradation
Infection
Interleukin-13
Coinfection
Interleukin-4
Developing Countries
Small Intestine
infection
Mucous Membrane
Vaccination
Up-Regulation
Animal Models
animals
mice

Keywords

  • mucosal trapping
  • Nippostrongylus brasiliensis
  • STAT6
  • TH2

ASJC Scopus subject areas

  • Parasitology
  • Animal Science and Zoology
  • Infectious Diseases

Cite this

Mucosal trapping and degradation of Nippostrongylus brasiliensis occurs in the absence of STAT6. / Van Panhuys, Nicholas J.; Camberis, Mali; Yamada, Minoru; Tegoshi, Tatsuya; Arizono, Naoki; Le Gros, Graham.

In: Parasitology, Vol. 140, No. 7, 06.2013, p. 833-843.

Research output: Contribution to journalArticle

Van Panhuys, Nicholas J. ; Camberis, Mali ; Yamada, Minoru ; Tegoshi, Tatsuya ; Arizono, Naoki ; Le Gros, Graham. / Mucosal trapping and degradation of Nippostrongylus brasiliensis occurs in the absence of STAT6. In: Parasitology. 2013 ; Vol. 140, No. 7. pp. 833-843.
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