Enteric nematodes induce stereotypic STAT6-dependent alterations in intestinal epithelial cell function.
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.
Madden
Kathleen B
KB
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Yeung
Karla Au
KA
Zhao
Aiping
A
Gause
William C
WC
Finkelman
Fred D
FD
Katona
Ildy M
IM
Urban
Joseph F
JF
Shea-Donohue
Terez
T
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
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D013779:Tetrodotoxin; D012964:Sodium; D005947:Glucose