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Immunity. 1999 Nov;11(5):637-47.

Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology.

Author information

1
Immunobiology Laboratory, Imperial Cancer Research Fund, London, United Kingdom. caetano@icrf.icnet.uk

Abstract

Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFNgamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFNgamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology.

PMID:
10591188
DOI:
10.1016/s1074-7613(00)80138-7
[Indexed for MEDLINE]
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