IL-4 independent nuclear translocalization of STAT6 in HeLa cells by entry of Toxoplasma gondii.
Toxoplasma gondii provokes rapid and sustained nuclear translocation of the signal transducer and activator of transcription 6 (STAT6) in HeLa cells. We observed activation of STAT6 as early as 2 hr after infection with T. gondii by the nuclear translocation of fluorescence expressed from exogenously transfected pDsRed2-STAT6 plasmid and by the detection of phosphotyrosine-STAT6 in Western blot. STAT6 activation occurred only by infection with live tachyzoites but not by co-culture with killed tachyzoites or soluble T. gondii extracts. STAT6 phosphorylation was inhibited by small interfering RNA of STAT6 (siSTAT6). In view of the fact that STAT6 is a central mediator of IL-4 induced gene expression, activation of STAT6 by T. gondii infection resembles that infected host cells has been stimulated by IL-4 treatment. STAT1 was affected to increase the transcription and expression by the treatment of siSTAT6. STAT6 activation was not affected by any excess SOCS's whereas that with IL-4 was inhibited by SOCS-1 and SOCS-3. T. gondii infection induced Eotaxin-3 gene expression which was reduced by IFN-gamma. These results demonstrate that T. gondii exploits host STAT6 to take away various harmful reactions by IFN-gamma. This shows, for the first time, IL-4-like action by T. gondii infection modulates microbicidal action by IFN-gamma in infected cells.
Ahn
Hye-Jin
HJ
Department of Parasitology and Catholic Institute of Parasitic Diseases, College of Medicine, Catholic University of Korea, Seoul, Korea.
Kim
Ji Yeon
JY
Nam
Ho-Woo
HW
D021581:Active Transport, Cell Nucleus; D000818:Animals; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor / Q000276:immunology* / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology*
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4