title: Mucosal trapping and degradation of Nippostrongylus brasiliensis occurs in the absence of STAT6.
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.
authors: Laboratory of Systems Biology, NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. vanpanhuysn@niaid.nih.gov
authors: Nicholas
authors: N
authors: Van Panhuys
authors: Mali
authors: M
authors: Camberis
authors: Minoru
authors: M
authors: Yamada
authors: Tatsuya
authors: T
authors: Tegoshi
authors: Naoki
authors: N
authors: Arizono
authors: Graham
authors: G
authors: Le Gros
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000235:genetics / Q000276:immunology*; D018510:RNA, Helminth / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology*
chemical_list: D018510:RNA, Helminth; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse