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Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its soluble polysaccharide fraction in a type I hypersensitivity murine model: induction of different activation status of antigen-presenting cells.

Squaiella-Baptistão CC, Teixeira D, Mussalem JS, Ishimura ME, Longo-Maugéri IM - J Immunol Res (2015)

Bottom Line: Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions.Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs).In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunoquímica, Instituto Butantan, Avenida Vital Brazil 1500, Prédio Novo, 2° Andar, Butantã, 05503-900 São Paulo, SP, Brazil.

ABSTRACT
Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model.

No MeSH data available.


Related in: MedlinePlus

Cytokines synthesis by spleen antigen-presenting cells. Spleen cells from mice treated with saline (Sal), P. acnes (Pa), or PS were obtained 14 days after HEW implantation and stained with fluorochrome-conjugated monoclonal anti-mouse antibodies to determine the intracellular synthesis of IL-4 and IL-12 by B lymphocytes, macrophages, and dendritic cells. Percentages obtained by flow cytometric analysis were converted to absolute numbers of B lymphocytes, macrophages, and dendritic cells positive for each cytokine, which were added to obtain the total number of spleen APCs positive for such cytokine in Protocols 1 (a) and 2 (e). Production levels were also determined by mean fluorescence intensity (MFI) and individually analyzed in B lymphocytes ((b) and (f)), macrophages ((c) and (g)), and dendritic cells ((d) and (h)) for Protocols 1 and 2, respectively. *P < 0.05; **P < 0.01; ***P < 0.0001.
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fig4: Cytokines synthesis by spleen antigen-presenting cells. Spleen cells from mice treated with saline (Sal), P. acnes (Pa), or PS were obtained 14 days after HEW implantation and stained with fluorochrome-conjugated monoclonal anti-mouse antibodies to determine the intracellular synthesis of IL-4 and IL-12 by B lymphocytes, macrophages, and dendritic cells. Percentages obtained by flow cytometric analysis were converted to absolute numbers of B lymphocytes, macrophages, and dendritic cells positive for each cytokine, which were added to obtain the total number of spleen APCs positive for such cytokine in Protocols 1 (a) and 2 (e). Production levels were also determined by mean fluorescence intensity (MFI) and individually analyzed in B lymphocytes ((b) and (f)), macrophages ((c) and (g)), and dendritic cells ((d) and (h)) for Protocols 1 and 2, respectively. *P < 0.05; **P < 0.01; ***P < 0.0001.

Mentions: Confirming the potentiation of the Th2 response to OVA, an increase in the number of spleen APCs synthesizing IL-4 in mice treated with P. acnes or PS according to Protocol 1 was observed, with a concomitant decrease in the number of IL-12+ cells (Figure 4(a)). Interestingly, P. acnes induced lower levels of these two cytokines on B lymphocytes and dendritic cells (Figures 4(b) and 4(d)) but increased the production of IL-12 by macrophages (Figure 4(c)). On the other hand, PS increased the production of IL-4 and IL-12 by macrophages and dendritic cells (Figures 4(c) and 4(d)).


Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its soluble polysaccharide fraction in a type I hypersensitivity murine model: induction of different activation status of antigen-presenting cells.

Squaiella-Baptistão CC, Teixeira D, Mussalem JS, Ishimura ME, Longo-Maugéri IM - J Immunol Res (2015)

Cytokines synthesis by spleen antigen-presenting cells. Spleen cells from mice treated with saline (Sal), P. acnes (Pa), or PS were obtained 14 days after HEW implantation and stained with fluorochrome-conjugated monoclonal anti-mouse antibodies to determine the intracellular synthesis of IL-4 and IL-12 by B lymphocytes, macrophages, and dendritic cells. Percentages obtained by flow cytometric analysis were converted to absolute numbers of B lymphocytes, macrophages, and dendritic cells positive for each cytokine, which were added to obtain the total number of spleen APCs positive for such cytokine in Protocols 1 (a) and 2 (e). Production levels were also determined by mean fluorescence intensity (MFI) and individually analyzed in B lymphocytes ((b) and (f)), macrophages ((c) and (g)), and dendritic cells ((d) and (h)) for Protocols 1 and 2, respectively. *P < 0.05; **P < 0.01; ***P < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4418006&req=5

fig4: Cytokines synthesis by spleen antigen-presenting cells. Spleen cells from mice treated with saline (Sal), P. acnes (Pa), or PS were obtained 14 days after HEW implantation and stained with fluorochrome-conjugated monoclonal anti-mouse antibodies to determine the intracellular synthesis of IL-4 and IL-12 by B lymphocytes, macrophages, and dendritic cells. Percentages obtained by flow cytometric analysis were converted to absolute numbers of B lymphocytes, macrophages, and dendritic cells positive for each cytokine, which were added to obtain the total number of spleen APCs positive for such cytokine in Protocols 1 (a) and 2 (e). Production levels were also determined by mean fluorescence intensity (MFI) and individually analyzed in B lymphocytes ((b) and (f)), macrophages ((c) and (g)), and dendritic cells ((d) and (h)) for Protocols 1 and 2, respectively. *P < 0.05; **P < 0.01; ***P < 0.0001.
Mentions: Confirming the potentiation of the Th2 response to OVA, an increase in the number of spleen APCs synthesizing IL-4 in mice treated with P. acnes or PS according to Protocol 1 was observed, with a concomitant decrease in the number of IL-12+ cells (Figure 4(a)). Interestingly, P. acnes induced lower levels of these two cytokines on B lymphocytes and dendritic cells (Figures 4(b) and 4(d)) but increased the production of IL-12 by macrophages (Figure 4(c)). On the other hand, PS increased the production of IL-4 and IL-12 by macrophages and dendritic cells (Figures 4(c) and 4(d)).

Bottom Line: Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions.Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs).In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunoquímica, Instituto Butantan, Avenida Vital Brazil 1500, Prédio Novo, 2° Andar, Butantã, 05503-900 São Paulo, SP, Brazil.

ABSTRACT
Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model.

No MeSH data available.


Related in: MedlinePlus