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- W4231997072 abstract "Infection with Leishmania, an obligate intracellular parasite of mononuclear phagocytes, stimulates the production of IFN-γ from NK cells, via a pathway which is dependent upon IL-12 and IL-2. IL-12 is also essential for the development of host protective T cell responses to this parasite. However, previous in vitro studies have indicated that macrophages fail to make IL-12 following infection with Leishmania, and that subsequent to infection, macrophages become refractory to normal IL-12-inducing stimuli. We have used an in situ approach to attempt to resolve this apparent paradox, and by immunostaining for IL-12 p40 protein, we now demonstrate for the first time, that dendritic cells (DC) are the critical source of early IL-12 production following Leishmania infection. IL-12 production by DC is transient, peaking at 1 day post infection and returning to the levels seen in uninfected mice by day 3. Although resident tissue macrophages fail to produce IL-12 after Leishmania infection, these cells are not totally refractory to cytokine inducing stimuli, as TNF-α production is induced by day 3 post infection. Not only do these data satisfactorily explain the dfferences between in vivo and in vitro data by identifying the cellular source of IL-12, but they also suggest a novel model for NK cell activation; namely that in response to pathogens which fail to trigger IL-12 production by macrophages, DC-T cell clusters provide the microenvironment for initial NK cell activation." @default.
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- W4231997072 date "1998-02-01" @default.
- W4231997072 modified "2023-10-05" @default.
- W4231997072 title "Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection" @default.
- W4231997072 doi "https://doi.org/10.1002/(sici)1521-4141(199802)28:02<687::aid-immu687>3.3.co;2-e" @default.
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