PMID- 31844885
OWN - NLM
STAT- MEDLINE
DCOM- 20210401
LR  - 20210401
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 222
IP  - 12
DP  - 2020 Nov 13
TI  - A Praziquantel Treatment Study of Immune and Transcriptome Profiles in 
      Schistosoma haematobium-Infected Gabonese Schoolchildren.
PG  - 2103-2113
LID - 10.1093/infdis/jiz641 [doi]
AB  - BACKGROUND: Although Schistosoma haematobium infection has been reported to be 
      associated with alterations in immune function, in particular immune 
      hyporesponsiveness, there have been only few studies that have used the approach 
      of removing infection by drug treatment to establish this and to understand the 
      underlying molecular mechanisms. METHODS: Schistosoma haematobium-infected 
      schoolchildren were studied before and after praziquantel treatment and compared 
      with uninfected controls. Cellular responses were characterized by cytokine 
      production and flow cytometry, and in a subset of children RNA sequencing 
      (RNA-Seq) transcriptome profiling was performed. RESULTS: Removal of S 
      haematobium infection resulted in increased schistosome-specific cytokine 
      responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and 
      accompanied by increased frequency of effector memory T-cells. Innate responses 
      to Toll like receptor (TLR) ligation decreased with treatment and showed positive 
      association with CD4+CD25+FOXP3+ T-cells. At the transcriptome level, schistosome 
      infection was associated with enrichment in cell adhesion, whereas parasite 
      removal was associated with a more quiescent profile. Further analysis indicated 
      that alteration in cellular energy metabolism was associated with S haematobium 
      infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), 
      transcription factors that negatively regulate T-cell activation, may play a role 
      in adaptive immune hyporesponsiveness. CONCLUSIONS: Using a longitudinal study 
      design, we found contrasting effects of schistosome infection on innate and 
      adaptive immune responses. Whereas the innate immune system appears more 
      activated, the adaptive immunity is in a hyporesponsive state reflected in 
      alterations in CD4+CD25+FOXP3+ T-cells, cellular metabolism, and transcription 
      factors involved in anergy.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Labuda, Lucja A
AU  - Labuda LA
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
AD  - Institut fur Tropenmedizin, Universitat Tubingen, Tubingen, Germany.
FAU - Adegnika, Ayola A
AU  - Adegnika AA
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
AD  - Institut fur Tropenmedizin, Universitat Tubingen, Tubingen, Germany.
FAU - Rosa, Bruce A
AU  - Rosa BA
AD  - McDonnell Genome Institute, Washington University in St. Louis, St. Louis, 
      Missouri, USA.
FAU - Martin, John
AU  - Martin J
AD  - McDonnell Genome Institute, Washington University in St. Louis, St. Louis, 
      Missouri, USA.
FAU - Ateba-Ngoa, Ulysse
AU  - Ateba-Ngoa U
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
AD  - Institut fur Tropenmedizin, Universitat Tubingen, Tubingen, Germany.
FAU - Amoah, Abena Serwaa
AU  - Amoah AS
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Department of Parasitology, Noguchi Memorial Institute for Medical Research, 
      University of Ghana, Legon, Accra, Ghana.
FAU - Lima, Honorine Mbenkep
AU  - Lima HM
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
AD  - Institut fur Tropenmedizin, Universitat Tubingen, Tubingen, Germany.
FAU - Meurs, Lynn
AU  - Meurs L
AD  - Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, 
      Belgium.
FAU - Mbow, Moustapha
AU  - Mbow M
AD  - Service d'Immunologie du Departement de Pharmacie, FMPO, Universite Cheikh Anta 
      Diop, Fann- Dakar, Senegal.
FAU - Manurung, Mikhael D
AU  - Manurung MD
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Zinsou, Jeannot F
AU  - Zinsou JF
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
FAU - Smits, Hermelijn H
AU  - Smits HH
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kremsner, Peter G
AU  - Kremsner PG
AD  - Centre de Recherches Medicales de Lambarene (CERMEL), Lambarene, Gabon.
AD  - Institut fur Tropenmedizin, Universitat Tubingen, Tubingen, Germany.
FAU - Mitreva, Makedonka
AU  - Mitreva M
AD  - McDonnell Genome Institute, Washington University in St. Louis, St. Louis, 
      Missouri, USA.
AD  - Division of Infectious Diseases, Department of Medicine, Washington University 
      School of Medicine, St. Louis, Missouri, USA.
FAU - Yazdanbakhsh, Maria
AU  - Yazdanbakhsh M
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anthelmintics)
RN  - 0 (Cytokines)
RN  - 6490C9U457 (Praziquantel)
SB  - IM
MH  - Adaptive Immunity
MH  - Animals
MH  - Anthelmintics/*therapeutic use
MH  - Child
MH  - Cytokines/*immunology
MH  - Female
MH  - Flow Cytometry
MH  - Gabon/epidemiology
MH  - Humans
MH  - Immunity, Innate
MH  - Longitudinal Studies
MH  - Male
MH  - Praziquantel/*therapeutic use
MH  - RNA-Seq
MH  - Schistosomiasis haematobia/drug therapy/*immunology
MH  - *Transcriptome
PMC - PMC7661769
OTO - NOTNLM
OT  - Schistosoma haematobium
OT  - CD4+CD25+FOXP3+ T-cells
OT  - cytokines
OT  - praziquantel
EDAT- 2019/12/18 06:00
MHDA- 2021/04/02 06:00
PMCR- 2019/12/17
CRDT- 2019/12/18 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2019/12/15 00:00 [accepted]
PHST- 2019/12/18 06:00 [pubmed]
PHST- 2021/04/02 06:00 [medline]
PHST- 2019/12/18 06:00 [entrez]
PHST- 2019/12/17 00:00 [pmc-release]
AID - 5679496 [pii]
AID - jiz641 [pii]
AID - 10.1093/infdis/jiz641 [doi]
PST - ppublish
SO  - J Infect Dis. 2020 Nov 13;222(12):2103-2113. doi: 10.1093/infdis/jiz641.