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Plasticity of migrating CD1b+ and CD1b- lymph dendritic cells in the promotion of Th1, Th2 and Th17 in response to Salmonella and helminth secretions.

Olivier M, Foret B, Le Vern Y, Kerboeuf D, Guilloteau LA - PLoS ONE (2013)

Bottom Line: The other major population of L-DCs did not express the CD1b molecule and displayed phenotypic features of immaturity compared to 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.

View Article: PubMed Central - PubMed

Affiliation: UR1282 Infectiologie et Santé Publique, INRA, Nouzilly, France.

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.

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Cytokine response of CD1b- L-DCs to Salmonella and helminth secretions.Production of cytokines was expressed as relative quantity ratios of RT-qPCR performed on mRNA extracted from cells incubated with Salmonella or Hc-ES for 6h. Data express the median (quartiles) from three sheep. (*) significantly different.
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pone-0079537-g003: Cytokine response of CD1b- L-DCs to Salmonella and helminth secretions.Production of cytokines was expressed as relative quantity ratios of RT-qPCR performed on mRNA extracted from cells incubated with Salmonella or Hc-ES for 6h. Data express the median (quartiles) from three sheep. (*) significantly different.

Mentions: In contrast to CD1b+ L-DCs, CD1b- L-DCs constitutively produced TNF-α, IL-23 and IL-4 mRNA (Figure 3 A). This constitutive production of TNF-α and IL-4 reduced significantly 6h after Salmonella infection, whereas it was maintained 6h after Hc-ES stimulation (Figure 3A, 3B), and then decreased 12h later (data not shown). The CD1b- L-DCs did not express Notch ligands Jagged-1 and Delta-4 mRNA but constitutively expressed the transcription factor GATA-3 mRNA, whose production tended to fall after Salmonella infection (data not shown).


Plasticity of migrating CD1b+ and CD1b- lymph dendritic cells in the promotion of Th1, Th2 and Th17 in response to Salmonella and helminth secretions.

Olivier M, Foret B, Le Vern Y, Kerboeuf D, Guilloteau LA - PLoS ONE (2013)

Cytokine response of CD1b- L-DCs to Salmonella and helminth secretions.Production of cytokines was expressed as relative quantity ratios of RT-qPCR performed on mRNA extracted from cells incubated with Salmonella or Hc-ES for 6h. Data express the median (quartiles) from three sheep. (*) significantly different.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818231&req=5

pone-0079537-g003: Cytokine response of CD1b- L-DCs to Salmonella and helminth secretions.Production of cytokines was expressed as relative quantity ratios of RT-qPCR performed on mRNA extracted from cells incubated with Salmonella or Hc-ES for 6h. Data express the median (quartiles) from three sheep. (*) significantly different.
Mentions: In contrast to CD1b+ L-DCs, CD1b- L-DCs constitutively produced TNF-α, IL-23 and IL-4 mRNA (Figure 3 A). This constitutive production of TNF-α and IL-4 reduced significantly 6h after Salmonella infection, whereas it was maintained 6h after Hc-ES stimulation (Figure 3A, 3B), and then decreased 12h later (data not shown). The CD1b- L-DCs did not express Notch ligands Jagged-1 and Delta-4 mRNA but constitutively expressed the transcription factor GATA-3 mRNA, whose production tended to fall after Salmonella infection (data not shown).

Bottom Line: The other major population of L-DCs did not express the CD1b molecule and displayed phenotypic features of immaturity compared to 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.

View Article: PubMed Central - PubMed

Affiliation: UR1282 Infectiologie et Santé Publique, INRA, Nouzilly, France.

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.

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Related in: MedlinePlus