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Eur Cytokine Netw. 1998 Sep;9(3 Suppl):65-8.

Ignition of the type 1 response to intracellular infection by dendritic cell-derived interleukin-12.

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Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


Host resistance to many intracellular pathogens is dependent on the induction of host IFN-gamma. This response in turn is triggered by the critical initiation cytokine, IL-12. Activated macrophages provide a major source of IL-12 during infection yet are unlikely to be the initial cell to produce the cytokine because of their need for IFN-gamma priming and/or other co-stimulatory signals. We have utilized an in vivo approach to identify the primary IL-12 producing cells which respond to the intracellular protozoan Toxoplasma gondii. Our results indicate that in spleen interdigitating dendritic cells (IDC) but not macrophages rapidly synthesize IL-12 after injection of parasite products or live tachyzoites. This response is both IFN-gamma and T lymphocyte independent. The same microbial stimulus results in the migration of IDC precursors into T cell areas and the upregulation of co-stimulatory cell-surface molecules. We postulate that these early dendritic cell activation events represent the "ignition switch" for the subsequent Type 1 cytokine response which leads to control of infection.

[Indexed for MEDLINE]

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