PMID- 19956564
OWN - NLM
STAT- MEDLINE
DCOM- 20100223
LR  - 20211020
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 3
IP  - 12
DP  - 2009 Dec 1
TI  - Identification of the Schistosoma mansoni TNF-alpha receptor gene and the effect 
      of human TNF-alpha on the parasite gene expression profile.
PG  - e556
LID - 10.1371/journal.pntd.0000556 [doi]
LID - e556
AB  - BACKGROUND: Schistosoma mansoni is the major causative agent of schistosomiasis. 
      The parasite takes advantage of host signals to complete its development in the 
      human body. Tumor necrosis factor-alpha (TNF-alpha) is a human cytokine involved 
      in skin inflammatory responses, and although its effect on the adult parasite's 
      metabolism and egg-laying process has been previously described, a comprehensive 
      assessment of the TNF-alpha pathway and its downstream molecular effects is 
      lacking. METHODOLOGY/PRINCIPAL FINDINGS: In the present work we describe a 
      possible TNF-alpha receptor (TNFR) homolog gene in S. mansoni (SmTNFR). SmTNFR 
      encodes a complete receptor sequence composed of 599 amino acids, and contains 
      four cysteine-rich domains as described for TNFR members. Real-time RT-PCR 
      experiments revealed that SmTNFR highest expression level is in cercariae, 3.5 
      (+/-0.7) times higher than in adult worms. Downstream members of the known human 
      TNF-alpha pathway were identified by an in silico analysis, revealing a possible 
      TNF-alpha signaling pathway in the parasite. In order to simulate parasite's 
      exposure to human cytokine during penetration of the skin, schistosomula were 
      exposed to human TNF-alpha just 3 h after cercariae-to-schistosomula in vitro 
      transformation, and large-scale gene expression measurements were performed with 
      microarrays. A total of 548 genes with significantly altered expression were 
      detected, when compared to control parasites. In addition, treatment of adult 
      worms with TNF-alpha caused a significantly altered expression of 1857 genes. 
      Interestingly, the set of genes altered in adults is different from that of 
      schistosomula, with 58 genes in common, representing 3% of altered genes in 
      adults and 11% in 3 h-old early schistosomula. CONCLUSIONS/SIGNIFICANCE: We 
      describe the possible molecular elements and targets involved in human TNF-alpha 
      effect on S. mansoni, highlighting the mechanism by which recently transformed 
      schistosomula may sense and respond to this host mediator at the site of 
      cercarial penetration into the skin.
FAU - Oliveira, Katia C
AU  - Oliveira KC
AD  - Laboratory of Gene Expression in Eukaryotes, Departamento de Bioquimica, 
      Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Carvalho, Mariana L P
AU  - Carvalho ML
FAU - Venancio, Thiago M
AU  - Venancio TM
FAU - Miyasato, Patricia A
AU  - Miyasato PA
FAU - Kawano, Toshie
AU  - Kawano T
FAU - DeMarco, Ricardo
AU  - DeMarco R
FAU - Verjovski-Almeida, Sergio
AU  - Verjovski-Almeida S
LA  - eng
SI  - GENBANK/GQ222226
SI  - GEO/GPL4791
SI  - GEO/GPL8606
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091201
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Helminth Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation/drug effects
MH  - Helminth Proteins/chemistry/*genetics/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - Receptors, Tumor Necrosis Factor, Type I/chemistry/*genetics/metabolism
MH  - Schistosoma mansoni/chemistry/classification/*genetics/metabolism
MH  - Schistosomiasis mansoni/*immunology/parasitology
MH  - Sequence Alignment
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*immunology/pharmacology
PMC - PMC2779652
COIS- The authors have declared that no competing interests exist.
EDAT- 2009/12/04 06:00
MHDA- 2010/02/24 06:00
PMCR- 2009/12/01
CRDT- 2009/12/04 06:00
PHST- 2009/06/01 00:00 [received]
PHST- 2009/10/20 00:00 [accepted]
PHST- 2009/12/04 06:00 [entrez]
PHST- 2009/12/04 06:00 [pubmed]
PHST- 2010/02/24 06:00 [medline]
PHST- 2009/12/01 00:00 [pmc-release]
AID - 09-PNTD-RA-0257R2 [pii]
AID - 10.1371/journal.pntd.0000556 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2009 Dec 1;3(12):e556. doi: 10.1371/journal.pntd.0000556.