PMID- 25314914
OWN - NLM
STAT- MEDLINE
DCOM- 20150508
LR  - 20220311
IS  - 1471-2334 (Electronic)
IS  - 1471-2334 (Linking)
VI  - 14
DP  - 2014 Oct 16
TI  - Phenotypic and functional evaluations of peripheral blood monocytes from 
      chronic-form paracoccidioidomycosis patients before and after treatment.
PG  - 552
LID - 10.1186/s12879-014-0552-x [doi]
LID - 552
AB  - BACKGROUND: Paracoccidioidomycosis (PCM) is systemic mycosis caused by the 
      thermal dimorphic fungus of genus Paracoccidioides, leading to either 
      acute/subacute (AF) or chronic (CF) clinical forms. Numerous CF patients after 
      treatment exhibit sequels, such as pulmonary and adrenal fibrosis. Monocytes are 
      cells that are involved in the inflammatory response during active infection as 
      well as in the fibrogenesis. These cells comprise a heterogeneous population with 
      distinct phenotypic and functional activities. The scope of this study was to 
      identify changes regarding functional and phenotypical aspects in monocytes 
      comparing CF PCM patients on antifungal treatment versus non-treated patients 
      (PMC-p). METHODS: Twenty-three CF PCM composed of 11 non-treated patients (NTG) 
      and 12 patients in apparent cure (ACG) were studied. Sixteen healthy individuals 
      were used as control group (CG). Monocyte subsets were determined by 
      immunophenotyping based on CD14 and CD16 expression. Cellular function was 
      measured in vitro with and without stimulation with lipopolysaccharide (LPS) and 
      P. brasiliensis exoantigen (PbAg) for 24 hours. Independent samples were compared 
      using unpaired t tests, dependent samples were analyzed by paired t-test. Groups 
      of more than two independent samples were analyzed using an ANOVA, with Tukey's 
      post-test. Significance was set up at p <0.05. RESULTS: Our results showed high 
      counts of peripheral blood CD14+CD16+ and CD14+CD16++ monocytes in untreated 
      PCM-p accompanied by intense production of pro-inflammatory cytokines (IL-1beta and 
      TNF-alpha) and profibrotic growth factors (TGF-beta1 and bFGF) by monocytes challenged 
      with P. brasiliensis antigens. After the introduction of antifungal therapy, the 
      counts of CD14+CD16+ cells returned to baseline while CD14+CD16++ counts remained 
      high. Interestingly, counts of CD14+CD16++ monocytes remained elevated even 
      52 +/- 7 months after successful antifungal treatment. Furthermore, the 
      ACG-patients showed preserved pro-inflammatory activity in the presence of 
      specific antigen stimuli and high spontaneous production of TNF-alpha by monocytes. 
      CONCLUSIONS: Infection with Paracoccidioides leads to initiation of a specific 
      proinflammatory response by monocytes of PCM-p during active disease and in the 
      apparent cure. A profibrotic profile by monocytes was observed only at admission. 
      Furthermore, PCM-p with apparent cure showed high spontaneous production of TNF-alpha 
      and high counts of CD14+CD16++ monocytes, probably induced by hypoxia duo to 
      fibrotic sequelae.
FAU - Venturini, James
AU  - Venturini J
FAU - Cavalcante, Ricardo Souza
AU  - Cavalcante RS
FAU - Golim, Marjorie de Assis
AU  - Golim Mde A
FAU - Marchetti, Camila Martins
AU  - Marchetti CM
FAU - Azevedo, Priscila Zacarias de
AU  - Azevedo PZ
FAU - Amorim, Barbara Casella
AU  - Amorim BC
FAU - Arruda, Maria Sueli Parreira de
AU  - Arruda MS
FAU - Mendes, Rinaldo Poncio
AU  - Mendes RP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141016
PL  - England
TA  - BMC Infect Dis
JT  - BMC infectious diseases
JID - 100968551
RN  - 0 (Antifungal Agents)
RN  - 0 (Cytokines)
RN  - 0 (FCGR3B protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Adult
MH  - Antifungal Agents/pharmacology/*therapeutic use
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Female
MH  - GPI-Linked Proteins/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/immunology/*metabolism
MH  - Paracoccidioidomycosis/blood/drug therapy/*immunology
MH  - Phenotype
MH  - Receptors, IgG/metabolism
PMC - PMC4201701
EDAT- 2014/10/16 06:00
MHDA- 2015/05/09 06:00
PMCR- 2014/10/16
CRDT- 2014/10/16 06:00
PHST- 2014/03/17 00:00 [received]
PHST- 2014/10/10 00:00 [accepted]
PHST- 2014/10/16 06:00 [entrez]
PHST- 2014/10/16 06:00 [pubmed]
PHST- 2015/05/09 06:00 [medline]
PHST- 2014/10/16 00:00 [pmc-release]
AID - s12879-014-0552-x [pii]
AID - 552 [pii]
AID - 10.1186/s12879-014-0552-x [doi]
PST - epublish
SO  - BMC Infect Dis. 2014 Oct 16;14:552. doi: 10.1186/s12879-014-0552-x.