Critical role for signal transducer and activator of transcription factor 6 in mediating intestinal muscle hypercontractility and worm expulsion in Trichinella spiralis-infected mice.
Intestinal nematode infections in rats or mice are accompanied by intestinal muscle hyper contractility that may contribute to parasite expulsion from the gut. Previous studies demonstrated that both the expulsion of nematode parasites and the associated muscle hyper contractility are dependent on CD4(+) T helper cells. Nevertheless, the precise immunological mechanism underlying changes in intestinal muscle function remains to be determined. In this study, we investigated the role of interleukin 4 (IL-4) and signal transducer and activator of transcription factor 6 (STAT6) in the development of intestinal muscle hypercontractility and worm expulsion by infecting IL-4 and STAT6-deficient mice with Trichinella spiralis. Worm expulsion was almost normal in IL-4-deficient mice but substantially delayed in STAT6-deficient mice. Consistent with delayed worm expulsion, we also observed a marked attenuation of carbachol-induced muscle contraction in STAT6-deficient mice but only a moderate decrease in muscle hypercontractility in IL-4-deficient mice. In addition, we also observed severe impairment of T helper type 2 cytokine responses and intestinal mucosal mastocytosis in STAT6-deficient mice, although some degree of intestinal tissue eosinophilia was evident in these animals. These results are consistent with the hypothesis that STAT6-dependent changes in intestinal muscle function contribute to host protection in nematode infection.
Khan
W I
WI
Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada.
Vallance
B A
BA
Blennerhassett
P A
PA
Deng
Y
Y
Verdu
E F
EF
Matthaei
K I
KI
Collins
S M
SM
D000818:Animals; D004802:Eosinophilia / Q000209:etiology; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007422:Intestines / Q000503:physiopathology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D050800:STAT6 Transcription Factor; D013154:Spleen / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology*; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology* / Q000503:physiopathology
D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4