Differential requirement of NF-kappa B family members in control of helminth infection and intestinal inflammation

D Artis, S Shapira, N Mason, K Speirs, M Goldschmidt, Jorge Caamano, H-C Liou, CA Hunter, P Scott

Research output: Contribution to journalArticle

73 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)4481-87
Number of pages7
JournalJournal of Immunology
Issue number8
Publication statusPublished - 1 Jan 2002


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