PMID- 19888805
OWN - NLM
STAT- MEDLINE
DCOM- 20100212
LR  - 20131213
IS  - 1460-2709 (Electronic)
IS  - 1369-3786 (Linking)
VI  - 47
IP  - 7
DP  - 2009 Nov
TI  - TLR-2, TLR-4 and dectin-1 expression in human monocytes and neutrophils 
      stimulated by Paracoccidioides brasiliensis.
PG  - 722-33
LID - 10.3109/13693780802641425 [doi]
AB  - Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the 
      dimorphic fungus Paracoccidioides brasiliensis. The pattern of the immune 
      responses to P. brasiliensis determines the disease progression and clinical 
      outcome. Innate immune response is mediated by phagocytic cells, such as 
      macrophage and neutrophils, which ingest and kill invading pathogens and then 
      trigger the adaptive immune system through the secretion of cytokines and 
      chemokines. The C-type like lectin receptors (CLR) and Toll-like receptors (TLRs) 
      are the two main pattern recognition receptors in phagocytic cells that recognize 
      fungal components. Therefore, the purpose of the present study was to evaluate 
      the expression of TLR-1, TLR-2, TLR-4 and dectin-1 (CLR) in monocytes and 
      neutrophils from healthy individuals after stimulation with Pb18 (high virulence) 
      and Pb265 (low virulence) yeasts of P. brasiliensis. As positive controls we used 
      specific ligands to TLR-4 (LPS), TLR-2 and dectin-1 (zymosan). Our results 
      demonstrated a decreased of TLRs and dectin-1 expression mainly on monocytes as 
      opposes on neutrophils, as soon as 30 minutes after yeast cells stimulation. This 
      decrease was similar to the one caused by zymosan stimulation and indicates that 
      up binding the complexes are rapidly internalized. There was a tendency towards 
      an increased TLR2 and dectin-1 mRNA expression in response to fungal cells, 
      mainly to Pb265. P. brasiliensis yeast cells induced the production of 
      pro-inflammatory and anti-inflammatory cytokines, but the low ratio between 
      TNF-alpha and IL-10 in response to zymosan and Pb265 indicates a balanced 
      production of IL-10 and TNF-alpha, while Pb18 predominantly induced TNF-alpha 
      secretion. Fungal cells also induced an elevated production of PGE(2) by 
      monocytes and neutrophils showing their potential to provoke an intense 
      inflammatory response. Altogether our results suggest the participation of TLR2, 
      TLR-4 and dectin-1 in P. brasiliensis recognition, internalization and consequent 
      activation of the immune response against the fungus. Moreover, the preferential 
      recognition of zymosan and Pb265 by TLR-2 and dectin-1 would result in the 
      production of adequate concentration of IL-10, which would be able to 
      counterbalance the excessive inflammatory response mediated by TNF-alpha and 
      PGE2. With these attributes the low virulence strain of P. brasiliensis would 
      induce a controlled immune response beneficial to the host.
FAU - Bonfim, Camila Vicente
AU  - Bonfim CV
AD  - Department of Clinical Pathology, Faculty of Medical Sciences, State University 
      of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil.
FAU - Mamoni, Ronei Luciano
AU  - Mamoni RL
FAU - Blotta, Maria Heloisa Souza Lima
AU  - Blotta MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Med Mycol
JT  - Medical mycology
JID - 9815835
RN  - 0 (IL10 protein, human)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (dectin 1)
RN  - 130068-27-8 (Interleukin-10)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Cells, Cultured
MH  - Dinoprostone/metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Interleukin-10/metabolism
MH  - Lectins, C-Type
MH  - Membrane Proteins/genetics/*metabolism
MH  - Monocytes/*immunology/microbiology
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neutrophils/*immunology/microbiology
MH  - Paracoccidioides/*physiology
MH  - RNA, Messenger/metabolism
MH  - Statistics, Nonparametric
MH  - Toll-Like Receptor 2/genetics/*metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2009/11/06 06:00
MHDA- 2010/02/13 06:00
CRDT- 2009/11/06 06:00
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2010/02/13 06:00 [medline]
AID - 10.3109/13693780802641425 [pii]
AID - 10.3109/13693780802641425 [doi]
PST - ppublish
SO  - Med Mycol. 2009 Nov;47(7):722-33. doi: 10.3109/13693780802641425.