Differential requirement for NF-kappa B family members in control of helminth infection and intestinal inflammation
The NF-kappaB family of transcription factors is critical in controlling the expression of a wide range of immune response genes. However, whether individual family members perform specific roles in regulating immunity and inflammation remains unclear. Here we investigated the requirement for NF-kap...
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Veröffentlicht in: | The Journal of immunology (1950) 2002-10, Vol.169 (8), p.4481-4487 |
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Sprache: | eng |
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Zusammenfassung: | The NF-kappaB family of transcription factors is critical in controlling the expression of a wide range of immune response genes. However, whether individual family members perform specific roles in regulating immunity and inflammation remains unclear. Here we investigated the requirement for NF-kappaB1, NF-kappaB2, and c-Rel in the expression of Th2 cytokine responses, development of host protective immunity, and regulation of intestinal inflammation following infection with the gut-dwelling helminth parasite Trichuris muris. While mice deficient in c-Rel mounted sufficient Th2 responses to expel infection, NF-kappaB1 knockout (KO) and NF-kappaB2 KO mice developed chronic infections associated with elevated production of Ag-specific IFN-gamma. However, only infected NF-kappaB1 KO mice exhibited polarized IFN-gamma responses associated with the loss of intestinal goblet cells and the development of destructive colitis-like pathology. Furthermore, blockade of IL-12 (previously shown to confer resistance in susceptible strains) recovered Ag-specific IL-13 responses and resistance to infection in NF-kappaB2 KO, but not NF-kappaB1 KO mice. Therefore, unique infection, immunological, and pathological outcomes were observed in different NF-kappaB KO strains. Taken together, these results provide direct evidence of nonoverlapping functions for NF-kappaB family members in the development of Th2 cytokine-mediated resistance to T. muris and the control of infection-induced intestinal inflammation. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.169.8.4481 |