PMID- 30761125
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20221124
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - The C-type Lectin Receptor-Driven, Th17 Cell-Mediated Severe Pathology in 
      Schistosomiasis: Not All Immune Responses to Helminth Parasites Are Th2 
      Dominated.
PG  - 26
LID - 10.3389/fimmu.2019.00026 [doi]
LID - 26
AB  - Schistosomiasis is a major helminthic disease in which damage to the affected 
      organs is orchestrated by a pathogenic host CD4 T helper (Th) cell-mediated 
      immune response against parasite eggs. In the case of the species Schistosoma 
      mansoni, the resulting granulomatous inflammation and fibrosis takes place in the 
      liver and intestines. The magnitude of disease varies greatly from individual to 
      individual but in a minority of patients, there is severe disease and death. S. 
      mansoni infection in a murine model similarly results in marked strain variation 
      of immunopathology. In the most commonly examined mouse strain, C57BL/6 (BL/6), 
      there is relatively mild hepatic pathology arising in a Th2-dominated cytokine 
      environment. In contrast, CBA mice develop decisively more severe lesions largely 
      driven by proinflammatory IL-17-producing Th17 cells. Dendritic cells (DCs) from 
      CBA mice differ sharply with those from BL/6 mice in that they vastly 
      over-express the C-type lectin receptor (CLR) CD209a (SIGNR5), a homolog of human 
      DC-SIGN, which senses glycans such as those produced by schistosome eggs. 
      Silencing of CD209a, and recent studies with CD209a KO CBA mice have shown that 
      this receptor is crucial to induce the pathogenic Th17 cell response; indeed, 
      CD209a KO mice display markedly reduced immunopathology akin to that seen in BL/6 
      mice. Mechanistically, CD209a synergizes with the related CLRs Dectin-2 and 
      Mincle to stimulate increased DC production of IL-1beta and IL-23, necessary for 
      pathogenic Th17 cell development. These findings denote key molecular 
      underpinnings of disease variability based on selection and function of 
      contrasting Th cell subsets.
FAU - Kalantari, Parisa
AU  - Kalantari P
AD  - Department of Immunology, Tufts University School of Medicine, Boston, MA, United 
      States.
FAU - Bunnell, Stephen C
AU  - Bunnell SC
AD  - Department of Immunology, Tufts University School of Medicine, Boston, MA, United 
      States.
FAU - Stadecker, Miguel J
AU  - Stadecker MJ
AD  - Department of Immunology, Tufts University School of Medicine, Boston, MA, United 
      States.
LA  - eng
GR  - R01 AI018919/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20190130
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytokines)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Cell Adhesion Molecules/metabolism
MH  - Cytokines/metabolism
MH  - Dendritic Cells/immunology/metabolism
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Host-Parasite Interactions/*immunology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Lectins, C-Type/*metabolism
MH  - Mice
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Schistosoma mansoni/immunology
MH  - Schistosomiasis/diagnosis/*immunology/*metabolism/parasitology
MH  - Severity of Illness Index
MH  - Th17 Cells/*immunology/*metabolism
MH  - Th2 Cells/immunology/metabolism
PMC - PMC6363701
OTO - NOTNLM
OT  - C-type lectin receptor
OT  - CD209a
OT  - DC-SIGN
OT  - Schistosoma mansoni
OT  - Th17 cells
OT  - immunopathology
EDAT- 2019/02/15 06:00
MHDA- 2019/12/21 06:00
PMCR- 2019/01/01
CRDT- 2019/02/15 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2019/01/08 00:00 [accepted]
PHST- 2019/02/15 06:00 [entrez]
PHST- 2019/02/15 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00026 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jan 30;10:26. doi: 10.3389/fimmu.2019.00026. eCollection 
      2019.