Abstract
Dendritic cells (DCs) are pivotal in the development of specific T-cell responses to control pathogens, as they govern both the initiation and the polarization of adaptive immunity. To investigate the capacities of migrating DCs to respond to pathogens, we used physiologically generated lymph DCs (L-DCs). The flexible polarization of L-DCs was analysed in response to Salmonella or helminth secretions known to induce different T cell responses. Mature conventional CD1b+ L-DCs showed a predisposition to promote pro-inflammatory (IL-6), pro-Th1 (IL-12p40) and anti-inflammatory (IL-10) responses which were amplified by Salmonella, and limited to only IL-6 induction by helminth secretions. The other major population of L-DCs did not express the CD1b molecule and displayed phenotypic features of immaturity compared to CD1b+ L-DCs. Salmonella infection reduced the constitutive expression of TNF-α and IL-4 mRNA in CD1b- L-DCs, whereas this expression was not affected by helminth secretions. The cytokine response of T cells promoted by L-DCs was analysed in T cell subsets after co-culture with Salmonella or helminth secretion-driven CD1b+ or CD1b- L-DCs. T cells preferentially expressed the IL-17 gene, and to a lesser extent the IFN-γ and IL-10 genes, in response to Salmonella-driven CD1b+ L-DCs, whereas a preferential IL-10, IFN-γ and IL-17 gene expression was observed in response to Salmonella-driven CD1b- L-DCs. In contrast, a predominant IL-4 and IL-13 gene expression by CD4+ and CD8+ T cells was observed after stimulation of CD1b+ and CD1b- L-DCs with helminth secretions. These results show that mature conventional CD1b+ L-DCs maintain a flexible capacity to respond differently to pathogens, that the predisposition of CD1b- L-DCs to promote a Th2 response can be oriented towards other Th responses, and finally that the modulation of migrating L-DCs responses is controlled more by the pathogen encountered than the L-DC subsets.
Highlights
Dendritic cells (DCs) are pivotal in the development of specific T-cell responses to control the diverse types of microorganisms that invade hosts, as they govern both the initiation and the polarization of adaptive immunity
The present study investigated in vitro the flexible capacity of physiologically generated lymph DCs (L-DCs) to respond to different pathogens, Salmonella and helminth secretions, and their impact on the promotion of the cytokine response in T cell subsets
In contrast to Salmonella, CD1b+ L-DCs driven by Hc-ES induced a very limited gene expression associated with a Th2 (IL-4 and IL-13) response by T cells
Summary
Dendritic cells (DCs) are pivotal in the development of specific T-cell responses to control the diverse types of microorganisms that invade hosts, as they govern both the initiation and the polarization of adaptive immunity. The current paradigm of DC-driven activation of naive Th cells is based on the requirement of three signals provided by pathogens interacting with DCs. The first results from pathogen-derived peptides, presented by MHC II on the DC cell surface, ligating to T-cell receptors, the second requires T-cell co-stimulation molecules, and the third depends on the Th polarizing capacities of DC-derived molecules [1]. The first results from pathogen-derived peptides, presented by MHC II on the DC cell surface, ligating to T-cell receptors, the second requires T-cell co-stimulation molecules, and the third depends on the Th polarizing capacities of DC-derived molecules [1] The expression of these molecules is dependent on and imprinted by the binding of pathogens to selective pattern recognition receptors (PRR) on immature DCs resulting in their programming during maturation. Migratory and lymphoid-organ-resident DC subsets with distinct functional abilities have been described [2,3]
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