title: Enteric nematodes induce stereotypic STAT6-dependent alterations in intestinal epithelial cell function.
abstract: Infection with gastrointestinal nematodes exerts profound effects on both the immune and physiological responses of the host. We showed previously that the Th2 cytokines, IL-4 and IL-13, induce STAT6-dependent changes in intestinal epithelial cell permeability, absorption, and secretion that are similar to those observed in a secondary infection with Heligmosomoides polygyrus. In the current study we investigated whether nematode-induced effects on epithelial cell function were 1) generic, 2) dependent upon STAT6, and 3) attributable to direct effects on the epithelial cells themselves or mediated by effects on enteric nerves. Our results demonstrate that infection of BALB/c mice with three different gastrointestinal nematodes (H. polygyrus, Nippostrongylus brasiliensis, and Trichinella spiralis) alters intestinal epithelial cell function by decreasing resistance, glucose absorption, and secretory responses to 5-hydroxytryptamine and acetylcholine, two critical mediators in the submucosal reflex pathway. These modified responses are dependent on STAT6 and are the result of both direct effects and indirect effects mediated through enteric nerves.
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Madden
authors.forename: Karla Au
authors.initials: KA
authors.lastname: Yeung
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhao
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Ildy M
authors.initials: IM
authors.lastname: Katona
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.forename: Terez
authors.initials: T
authors.lastname: Shea-Donohue
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D007408:Intestinal Absorption / Q000235:genetics / Q000276:immunology; D007411:Intestinal Diseases, Parasitic / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000294:innervation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009349:Nematode Infections / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D009351:Nematospiroides dubius / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology; D050800:STAT6 Transcription Factor; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017160:Trichinella spiralis / Q000276:immunology
chemical_list: D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D013779:Tetrodotoxin; D012964:Sodium; D005947:Glucose