PMID- 25965781
OWN - NLM
STAT- MEDLINE
DCOM- 20160218
LR  - 20190202
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 9
IP  - 5
DP  - 2015 May
TI  - An ex vivo model for studying hepatic schistosomiasis and the effect of released 
      protein from dying eggs.
PG  - e0003760
LID - 10.1371/journal.pntd.0003760 [doi]
LID - e0003760
AB  - BACKGROUND: We report the use of an ex vivo precision cut liver slice (PCLS) 
      mouse model for studying hepatic schistosomiasis. In this system, liver tissue is 
      unfixed, unfrozen, and alive for maintenance in culture and subsequent molecular 
      analysis. METHODS AND FINDINGS: Using thick naive mouse liver tissue and sterile 
      culture conditions, the addition of soluble egg antigen (SEA) derived from 
      Schistosoma japonicum eggs, followed 4, 24 and 48 hrs time points. Tissue was 
      collected for transcriptional analysis and supernatants collected to quantitate 
      liver enzymes, cytokines and chemokines. No significant hepatotoxicity was 
      demonstrated by supernatant liver enzymes due to the presence of SEA. A 
      proinflammatory response was observed both at the transcriptional level and at 
      the protein level by cytokine and chemokine bead assay. Key genes observed 
      elevated transcription in response to the addition of SEA included: IL1-alpha and 
      IL1-beta, IL6, all associated with inflammation. The recruitment of antigen 
      presenting cells was reflected in increases in transcription of CD40, CCL4 and 
      CSF1. Indications of tissue remodeling were seen in elevated gene expression of 
      various Matrix MetalloProteinases (MMP3, 9, 10, 13) and delayed increases in 
      TIMP1. Collagen deposition was significantly reduced in the presence of SEA as 
      shown in COL1A1 expression by qPCR after 24 hrs culture. Cytokine and chemokine 
      analysis of the culture supernatants confirmed the elevation of proteins 
      including IL6, CCL3, CCL4 and CXCL5. CONCLUSIONS: This ex vivo model system for 
      the synchronised delivery of parasite antigen to liver tissue provides an insight 
      into the early phase of hepatic schistosomiasis, corresponding with the release 
      of soluble proteins from dying schistosome eggs.
FAU - Gobert, Geoffrey N
AU  - Gobert GN
AD  - QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
FAU - Nawaratna, Sujeevi K
AU  - Nawaratna SK
AD  - QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
FAU - Harvie, Marina
AU  - Harvie M
AD  - QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
FAU - Ramm, Grant A
AU  - Ramm GA
AD  - QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
FAU - McManus, Donald P
AU  - McManus DP
AD  - QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antigens, Protozoan)
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CXCL5)
RN  - 0 (Cxcl5 protein, mouse)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Antigens, Protozoan/*immunology
MH  - CD40 Antigens/immunology
MH  - Chemokine CCL4/immunology
MH  - Chemokine CXCL5/immunology
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Inflammation/immunology/parasitology
MH  - Interleukin-1alpha/immunology
MH  - Interleukin-1beta/immunology
MH  - Interleukin-6/immunology
MH  - Liver/*parasitology
MH  - Liver Diseases, Parasitic/*immunology/parasitology
MH  - Macrophage Colony-Stimulating Factor/immunology
MH  - Mice
MH  - Ovum/*immunology
MH  - Schistosomiasis/*immunology/parasitology/pathology
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis
PMC - PMC4428699
COIS- The authors have declared that no competing interests exist.
EDAT- 2015/05/13 06:00
MHDA- 2016/02/19 06:00
PMCR- 2015/05/12
CRDT- 2015/05/13 06:00
PHST- 2015/01/27 00:00 [received]
PHST- 2015/04/14 00:00 [accepted]
PHST- 2015/05/13 06:00 [entrez]
PHST- 2015/05/13 06:00 [pubmed]
PHST- 2016/02/19 06:00 [medline]
PHST- 2015/05/12 00:00 [pmc-release]
AID - PNTD-D-15-00137 [pii]
AID - 10.1371/journal.pntd.0003760 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2015 May 12;9(5):e0003760. doi: 10.1371/journal.pntd.0003760. 
      eCollection 2015 May.