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Paracoccidioides brasiliensis interferes on dendritic cells maturation by inhibiting PGE2 production.

Fernandes RK, Bachiega TF, Rodrigues DR, Golim Mde A, Dias-Melicio LA, Balderramas Hde A, Kaneno R, Soares ÂM - PLoS ONE (2015)

Bottom Line: In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α.We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation.These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil.

ABSTRACT
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE2, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE2 inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE2 confirmed an association between PGE2 inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.

No MeSH data available.


Related in: MedlinePlus

Effect of exogenous PGE2 on TNF-α production by DCs challenged with Pb18 or Pb265 by 48 h and evaluated by ELISA.The results are expressed in mean ± SD of experiments performed with cells obtained from 4 subjects. Statistically significant differences between groups are indicated: *p< 0.05 versus without PGE2.
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pone.0120948.g006: Effect of exogenous PGE2 on TNF-α production by DCs challenged with Pb18 or Pb265 by 48 h and evaluated by ELISA.The results are expressed in mean ± SD of experiments performed with cells obtained from 4 subjects. Statistically significant differences between groups are indicated: *p< 0.05 versus without PGE2.

Mentions: In addition to modulation of DCs phenotype, exogenous PGE2 also promote alterations in TNF-α production (Fig. 6), whose levels after treatment were similar to those induced by LPS (Fig. 4). On other hand, DCs did not produce IL-12p70 even after exogenous PGE2 treatment. Taken together, data on DC phenotype and cytokine production suggest that P. brasiliensis fails to induce DC maturation, at least in part because PGE2 production is inhibited.


Paracoccidioides brasiliensis interferes on dendritic cells maturation by inhibiting PGE2 production.

Fernandes RK, Bachiega TF, Rodrigues DR, Golim Mde A, Dias-Melicio LA, Balderramas Hde A, Kaneno R, Soares ÂM - PLoS ONE (2015)

Effect of exogenous PGE2 on TNF-α production by DCs challenged with Pb18 or Pb265 by 48 h and evaluated by ELISA.The results are expressed in mean ± SD of experiments performed with cells obtained from 4 subjects. Statistically significant differences between groups are indicated: *p< 0.05 versus without PGE2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368678&req=5

pone.0120948.g006: Effect of exogenous PGE2 on TNF-α production by DCs challenged with Pb18 or Pb265 by 48 h and evaluated by ELISA.The results are expressed in mean ± SD of experiments performed with cells obtained from 4 subjects. Statistically significant differences between groups are indicated: *p< 0.05 versus without PGE2.
Mentions: In addition to modulation of DCs phenotype, exogenous PGE2 also promote alterations in TNF-α production (Fig. 6), whose levels after treatment were similar to those induced by LPS (Fig. 4). On other hand, DCs did not produce IL-12p70 even after exogenous PGE2 treatment. Taken together, data on DC phenotype and cytokine production suggest that P. brasiliensis fails to induce DC maturation, at least in part because PGE2 production is inhibited.

Bottom Line: In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α.We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation.These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil.

ABSTRACT
Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE2, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE2 inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE2 confirmed an association between PGE2 inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.

No MeSH data available.


Related in: MedlinePlus