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Publication : 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.

First Author  Demangel C Year  2002
Journal  Eur J Immunol Volume  32
Issue  4 Pages  994-1002
PubMed ID  11920565 Mgi Jnum  J:75998
Mgi Id  MGI:2178194 Doi  10.1002/1521-4141(200204)32:4<994::AID-IMMU994>3.0.CO;2-6
Citation  Demangel C, et al. (2002) 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. Eur J Immunol 32(4):994-1002
abstractText  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 Guerin (BCG) induced a concurrent and dose-dependent releaseof 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-gamma 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.
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