Ignition of the type 1 response to intracellular infection by dendritic cell-derived interleukin-12.
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.
Sher
A
A
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Reis e Sousa
C
C
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology
D018664:Interleukin-12