Expulsion of Trichuris muris is associated with increased expression of angiogenin 4 in the gut and increased acidity of mucins within the goblet cell.
BACKGROUND
Trichuris muris in the mouse is an invaluable model for infection of man with the gastrointestinal nematode Trichuris trichiura. Three T. muris isolates have been studied, the Edinburgh (E), the Japan (J) and the Sobreda (S) isolates. The S isolate survives to chronicity within the C57BL/6 host whereas E and J are expelled prior to reaching fecundity. How the S isolate survives so successfully in its host is unclear.


RESULTS
Microarray analysis was used as a tool to identify genes whose expression could determine the differences in expulsion kinetics between the E and S T. muris isolates. Clear differences in gene expression profiles were evident as early as day 7 post-infection (p.i.). 43 probe sets associated with immune and defence responses were up-regulated in gut tissue from an E isolate-infected C57BL/6 mouse compared to tissue from an S isolate infection, including the message for the anti-microbial protein, angiogenin 4 (Ang4). This led to the identification of distinct differences in the goblet cell phenotype post-infection with the two isolates.


CONCLUSIONS
Differences in gene expression levels identified between the S and E-infected mice early during infection have furthered our knowledge of how the S isolate persists for longer than the E isolate in the C57BL/6 mouse. Potential new targets for manipulation in order to aid expulsion have been identified. Further we provide evidence for a potential new marker involving the acidity of the mucins within the goblet cell which may predict outcome of infection within days of parasite exposure.
D'Elia
Riccardo
R
Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK. rvdelia@dstl.gov.uk
DeSchoolmeester
Matthew L
ML
Zeef
Leo A H
LA
Wright
Steven H
SH
Pemberton
Alan D
AD
Else
Kathryn J
KJ
D000818:Animals; D005752:Gastric Mucins / Q000737:chemistry* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D013997:Time Factors; D014258:Trichuris / Q000276:immunology*; D015854:Up-Regulation
D005752:Gastric Mucins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C519253:Ang4 protein, mouse; D012259:Ribonuclease, Pancreatic