Epithelial stem cell-related alterations in Trichinella spiralis-infected small intestine.
OBJECTIVE
Infection of mice with the parasite Trichinella spiralis leads to small intestinal inflammation, characterized by changes in mucosal architecture and subpopulations of epithelial cells. This model has been used to explore changes in the epithelial proliferative cell population and expression of transforming growth factor-beta (TGF-beta).


METHODS
Histochemical and immunohistochemical studies were undertaken in duodenal samples. Location and number of Ki-67-positive cells were assessed using Score and Wincrypts program. Changes in mRNA transcripts were studied by real-time RT-PCR.


RESULTS
T. spiralis infection induced an increase in total number of proliferative (Ki-67-positive) cells per half crypt on day 2 post-infection. Transcription of Math1, a transcription factor required for secretory cell differentiation in the intestine, was up-regulated on days 6-18 post-infection. At these time points, numbers of Paneth cells at the crypt base were also increased and the epithelial proliferative zone was shifted up the crypt-villus axis. Transcription of TGF-beta isoforms within the small intestine was up-regulated on days 6 and 12 post-infection, but anti-TGF-beta antibody treatment had no effect on T. spiralis-induced changes in mucosal architecture or increase in Paneth/intermediate cells.


CONCLUSIONS
T. spiralis infection promotes an initial increase in small intestinal epithelial proliferation and subsequent cell differentiation along the secretory cell lineage. The resulting increase in numbers of Paneth cells at the crypt base causes the proliferative zone to move up the crypt-villus axis. Further studies are required to determine the significance of an increase in the expression of TGF-beta transcripts.
Walsh
R
R
Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham, UK.
Seth
R
R
Behnke
J
J
Potten
C S
CS
Mahida
Y R
YR
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology*; D007421:Intestine, Small / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D017160:Trichinella spiralis / Q000472:pathogenicity*; D014235:Trichinellosis / Q000473:pathology*
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C500943:Atoh1 protein, mouse