Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production
✍ Scribed by Caroline Demangel; Patrick Bertolino; Warwick J. Britton
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 137 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
The production of IL-12 by dendritic cells (DC) early in an immune response is considered critical for the polarization of CD4 + T lymphocyte response towards a Th1 pattern, a key process in the clearance of intracellular pathogens. Infection of bone marrow-derived DC with Mycobacterium bovis Bacillus Calmette Gu érin (BCG) induced a concurrent and dosedependent release of IL-10 and IL-12. Here we examined whether the production of IL-10 by DC affected their IL-12 response to mycobacterial infection and the generation of protective immune responses in vivo. Compared to wild-type (WT) DC, DC deficient for IL-10 synthesis (IL-10 -/-) showed increased IL-12 production in response to BCG infection and CD40 stimuli in vitro. Moreover, when transferred into mice, infected IL-10 -/-DC were more efficient than WT DC at inducing IFN-+ production to mycobacterial antigens in the draining lymph nodes (DLN). This effect was associated with increased trafficking of IL-10 -/-DC to the DLN and enhanced IL-12 production by DC within the DLN. These data show that autocrine IL-10 exerts a dual inhibitory effect on the induction of primary immune responses by DC: first, by down-regulating the migration of infected DC to the DLN and second, by modulating the IL-12 production by DC in the DLN.