Investigating the Role of STAT1 Transcription Factor in the Regulation of Schistosome Immunopathology
Open Access
- Author:
- Yi, Sara
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Parisa Kalantari, Thesis Supervisor
Stephen Wade Schaeffer, Thesis Honors Advisor - Keywords:
- schistosome
mansoni
schistosomiasis
inflammation
inflammatory
stat1
stat3
infectious
disease
parasite
parasitic
worms
infect
interferon
ifn-1
ifn
cytokines
th2
th1
transcription factor
transcription
dendritic
cell
inflammasome
nlrp3
asc
il-10
il-1b
immunopathology
bmdc
cercariae
granule
fibrosis
trematode
immunology
immune - Abstract:
- Schistosomes are parasitic trematode worms that infest bodies of water and cause the disease schistosomiasis. A portion of eggs produced by adult schistosomula lodge in the liver and induce CD4 T helper (Th) cell-mediated granulomatous inflammation and fibrosis. Milder pathology is associated with T helper 2 (Th2) cytokines while severe pathology is associated with Th1 and Th17 cells. We have previously shown that Type I Interferon (IFN-I) plays a key role in controlling disease pathogenesis by limiting inflammation. Yet, it is unknown how interferon-α/β receptor (IFNAR) signaling impacts disease severity and which transcription factors are activated downstream of IFNAR. Previous studies showed that schistosome eggs are potent inducers of signal transducer and activator of transcription (STAT1) phosphorylation in Dendritic cells but revealed no consequences to this activation. We demonstrated that mechanistically STAT1 diminishes inflammation by restraining egg-mediated inflammasome activation and inducing anti-inflammatory cytokine production. Additionally, we showed that STAT1 deficiency results in marked increase in pathology in vivo. These results suggest that schistosome egg mediated STAT1 activation directly curbs inflammation and immunopathology in vitro and in vivo.