PMID- 25793979
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Paracoccidioides brasiliensis interferes on dendritic cells maturation by 
      inhibiting PGE2 production.
PG  - e0120948
LID - 10.1371/journal.pone.0120948 [doi]
LID - e0120948
AB  - 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-alpha. 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.
FAU - Fernandes, Reginaldo K
AU  - Fernandes RK
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Bachiega, Tatiana F
AU  - Bachiega TF
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Rodrigues, Daniela R
AU  - Rodrigues DR
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Golim, Marjorie de A
AU  - Golim Mde A
AD  - Flow Cytometry Laboratory, Hemocenter, Sao Paulo State University, UNESP, 
      Botucatu, Sao Paulo, Brazil.
FAU - Dias-Melicio, Luciane A
AU  - Dias-Melicio LA
AD  - Department of Pathology, Botucatu Medical School, Sao Paulo State University, 
      UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Balderramas, Helanderson de A
AU  - Balderramas Hde A
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Kaneno, Ramon
AU  - Kaneno R
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
FAU - Soares, Angela M V C
AU  - Soares AM
AD  - Department of Microbiology and Immunology, Biosciences Institute, Sao Paulo State 
      University, UNESP, Botucatu, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150320
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
EIN - PLoS One. 2015;10(6):e0131380. PMID: 26114288
MH  - Cell Count
MH  - *Cell Differentiation
MH  - Dendritic Cells/drug effects/*microbiology/*pathology
MH  - Dinoprostone/*biosynthesis/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescence
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Paracoccidioides/drug effects/*physiology
MH  - Phenotype
MH  - Receptors, Cell Surface/metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC4368678
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/21 06:00
MHDA- 2016/02/09 06:00
PMCR- 2015/03/20
CRDT- 2015/03/21 06:00
PHST- 2014/10/17 00:00 [received]
PHST- 2015/01/27 00:00 [accepted]
PHST- 2015/03/21 06:00 [entrez]
PHST- 2015/03/21 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
PHST- 2015/03/20 00:00 [pmc-release]
AID - PONE-D-14-46368 [pii]
AID - 10.1371/journal.pone.0120948 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 20;10(3):e0120948. doi: 10.1371/journal.pone.0120948. 
      eCollection 2015.