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Effects of the Staphylococcus aureus and Staphylococcus epidermidis Secretomes Isolated from the Skin Microbiota of Atopic Children on CD4+ T Cell Activation.

Laborel-Préneron E, Bianchi P, Boralevi F, Lehours P, Fraysse F, Morice-Picard F, Sugai M, Sato'o Y, Badiou C, Lina G, Schmitt AM, Redoulès D, Casas C, Davrinche C - PLoS ONE (2015)

Bottom Line: Monocyte-derived dendritic cells (moDC) exposed to the S. aureus and S. epidermidis secretomes were found to release pro-inflammatory IFN-γ and anti-inflammatory IL-10, respectively.We therefore conclude that S. aureus may cause and promote inflammation in the skin of AD children through concomitant Th2 activation and the silencing of resident Treg cells.Commensals such as S. epidermidis may counteract these effects by inducing the release of IL-10 by skin dendritic cells.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.

ABSTRACT
Interactions between the immune system and skin bacteria are of major importance in the pathophysiology of atopic dermatitis (AD), yet our understanding of them is limited. From a cohort of very young AD children (1 to 3 years old), sensitized to Dermatophagoides pteronyssinus allergens (Der p), we conducted culturomic analysis of skin microbiota, cutaneous transcript profiling and quantification of anti-Der p CD4+ T cells. This showed that the presence of S. aureus in inflamed skin of AD patients was associated with a high IgE response, increased expression of inflammatory and Th2/Th22 transcripts and the prevalence of a peripheral Th2 anti-Der p response. Monocyte-derived dendritic cells (moDC) exposed to the S. aureus and S. epidermidis secretomes were found to release pro-inflammatory IFN-γ and anti-inflammatory IL-10, respectively. Allogeneic moDC exposed to the S. aureus secretome also induced the proliferation of CD4+ T cells and this effect was counteracted by concurrent exposure to the S. epidermidis secretome. In addition, whereas the S. epidermidis secretome promoted the activity of regulatory T cells (Treg) in suppressing the proliferation of conventional CD4+ T cells, the Treg lost this ability in the presence of the S. aureus secretome. We therefore conclude that S. aureus may cause and promote inflammation in the skin of AD children through concomitant Th2 activation and the silencing of resident Treg cells. Commensals such as S. epidermidis may counteract these effects by inducing the release of IL-10 by skin dendritic cells.

No MeSH data available.


Related in: MedlinePlus

IL-4-producing peripheral T CD4+ cells against Der p allergens are increased in AD children compared to IFN-γ- producing T CD4+ cells.(A) IFN-γ and IL-4 ELISPot assays (spot forming units/106 T cells) were performed on peripheral blood from non-AD (N = 14) and AD (N = 15) children in response to crude extracts of Der p. (B) Ratio of IL-4 vs IFN-γ CD4+ T cell spots relative to titers of total or Der p1 specific IgE antibodies (kU/ml) in AD patients. Mann-Whitney, mean values with SEM are shown, p*<0.05, p**<0.01.
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pone.0141067.g002: IL-4-producing peripheral T CD4+ cells against Der p allergens are increased in AD children compared to IFN-γ- producing T CD4+ cells.(A) IFN-γ and IL-4 ELISPot assays (spot forming units/106 T cells) were performed on peripheral blood from non-AD (N = 14) and AD (N = 15) children in response to crude extracts of Der p. (B) Ratio of IL-4 vs IFN-γ CD4+ T cell spots relative to titers of total or Der p1 specific IgE antibodies (kU/ml) in AD patients. Mann-Whitney, mean values with SEM are shown, p*<0.05, p**<0.01.

Mentions: These transcript analyses results are suggestive of a high rate of Th2 lymphocytes presence in the inflamed skin of AD children. Since T cells can continuously recirculate between the blood and inflamed lesions, and since we did not extract cells from the skin of children due to their age, we determined the phenotype of peripheral anti-Der p CD4+ T cells by IL-4 and IFN-γ ELISpots. Due to the small volumes of the available blood samples we were not able to analyze IL-22-producing CD4+ T cells. However, whereas CD4+ T cells co-cultured with autologous moDC pulsed with Der p allergens secreted IFN-γ in both AD and non-AD children, the number of IL-4-secreting-forming units was significantly higher in AD than non-AD children (Fig 2A). A prevalence of IL-4-secreting cells was observed in patients with Der p1-specific IgE>100 kUI/ml (Fig 2B) and this correlated with S. aureus counts (S1 Fig, Spearman’s correlation r = 0.63, p = 0.0062). As a whole, our analyses of the cutaneous microbiota, of transcript profiling and of the peripheral anti-Der p CD4+ T cell response in AD children have revealed a spectrum of clinical phenotypes including the colonization of inflammatory skin with S. aureus, defects in barrier integrity, inflammasome activation and leukocyte activation characterized by Th2/Th22 cells.


Effects of the Staphylococcus aureus and Staphylococcus epidermidis Secretomes Isolated from the Skin Microbiota of Atopic Children on CD4+ T Cell Activation.

Laborel-Préneron E, Bianchi P, Boralevi F, Lehours P, Fraysse F, Morice-Picard F, Sugai M, Sato'o Y, Badiou C, Lina G, Schmitt AM, Redoulès D, Casas C, Davrinche C - PLoS ONE (2015)

IL-4-producing peripheral T CD4+ cells against Der p allergens are increased in AD children compared to IFN-γ- producing T CD4+ cells.(A) IFN-γ and IL-4 ELISPot assays (spot forming units/106 T cells) were performed on peripheral blood from non-AD (N = 14) and AD (N = 15) children in response to crude extracts of Der p. (B) Ratio of IL-4 vs IFN-γ CD4+ T cell spots relative to titers of total or Der p1 specific IgE antibodies (kU/ml) in AD patients. Mann-Whitney, mean values with SEM are shown, p*<0.05, p**<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4624846&req=5

pone.0141067.g002: IL-4-producing peripheral T CD4+ cells against Der p allergens are increased in AD children compared to IFN-γ- producing T CD4+ cells.(A) IFN-γ and IL-4 ELISPot assays (spot forming units/106 T cells) were performed on peripheral blood from non-AD (N = 14) and AD (N = 15) children in response to crude extracts of Der p. (B) Ratio of IL-4 vs IFN-γ CD4+ T cell spots relative to titers of total or Der p1 specific IgE antibodies (kU/ml) in AD patients. Mann-Whitney, mean values with SEM are shown, p*<0.05, p**<0.01.
Mentions: These transcript analyses results are suggestive of a high rate of Th2 lymphocytes presence in the inflamed skin of AD children. Since T cells can continuously recirculate between the blood and inflamed lesions, and since we did not extract cells from the skin of children due to their age, we determined the phenotype of peripheral anti-Der p CD4+ T cells by IL-4 and IFN-γ ELISpots. Due to the small volumes of the available blood samples we were not able to analyze IL-22-producing CD4+ T cells. However, whereas CD4+ T cells co-cultured with autologous moDC pulsed with Der p allergens secreted IFN-γ in both AD and non-AD children, the number of IL-4-secreting-forming units was significantly higher in AD than non-AD children (Fig 2A). A prevalence of IL-4-secreting cells was observed in patients with Der p1-specific IgE>100 kUI/ml (Fig 2B) and this correlated with S. aureus counts (S1 Fig, Spearman’s correlation r = 0.63, p = 0.0062). As a whole, our analyses of the cutaneous microbiota, of transcript profiling and of the peripheral anti-Der p CD4+ T cell response in AD children have revealed a spectrum of clinical phenotypes including the colonization of inflammatory skin with S. aureus, defects in barrier integrity, inflammasome activation and leukocyte activation characterized by Th2/Th22 cells.

Bottom Line: Monocyte-derived dendritic cells (moDC) exposed to the S. aureus and S. epidermidis secretomes were found to release pro-inflammatory IFN-γ and anti-inflammatory IL-10, respectively.We therefore conclude that S. aureus may cause and promote inflammation in the skin of AD children through concomitant Th2 activation and the silencing of resident Treg cells.Commensals such as S. epidermidis may counteract these effects by inducing the release of IL-10 by skin dendritic cells.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.

ABSTRACT
Interactions between the immune system and skin bacteria are of major importance in the pathophysiology of atopic dermatitis (AD), yet our understanding of them is limited. From a cohort of very young AD children (1 to 3 years old), sensitized to Dermatophagoides pteronyssinus allergens (Der p), we conducted culturomic analysis of skin microbiota, cutaneous transcript profiling and quantification of anti-Der p CD4+ T cells. This showed that the presence of S. aureus in inflamed skin of AD patients was associated with a high IgE response, increased expression of inflammatory and Th2/Th22 transcripts and the prevalence of a peripheral Th2 anti-Der p response. Monocyte-derived dendritic cells (moDC) exposed to the S. aureus and S. epidermidis secretomes were found to release pro-inflammatory IFN-γ and anti-inflammatory IL-10, respectively. Allogeneic moDC exposed to the S. aureus secretome also induced the proliferation of CD4+ T cells and this effect was counteracted by concurrent exposure to the S. epidermidis secretome. In addition, whereas the S. epidermidis secretome promoted the activity of regulatory T cells (Treg) in suppressing the proliferation of conventional CD4+ T cells, the Treg lost this ability in the presence of the S. aureus secretome. We therefore conclude that S. aureus may cause and promote inflammation in the skin of AD children through concomitant Th2 activation and the silencing of resident Treg cells. Commensals such as S. epidermidis may counteract these effects by inducing the release of IL-10 by skin dendritic cells.

No MeSH data available.


Related in: MedlinePlus