Immunomodulation in the canine endometrium by uteropathogenic Escherichia coli.
- 1Reproduction and Development Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
- 2Pathology Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
- 3Reproduction and Development Laboratory, CIISA, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal. lmateus@fmv.ulisboa.pt.
Abstract
This
study was designed to evaluate the role of E. coli α-hemolysin (HlyA)
in the pathogenesis of canine pyometra, and on the immune response of
canine endometrial epithelial and stromal cells. In Experiment 1, the
clinical, hematological, biochemical and uterine histological
characteristics of β-hemolytic and non-hemolytic E. coli pyometra
bitches were compared. More (p < 0.05) metritis cases were observed
in β-hemolytic E. coli pyometra uteri than in non-hemolytic E. coli
pyometra uteri. β-hemolytic E. coli pyometra endometria had higher gene
transcription of IL-1β and IL-8 and lower gene transcription of IL-6
than non-hemolytic E. coli pyometra endometria (p < 0.01). In
Experiment 2, the immune response of endometrial epithelial and stromal
cells, to hemolytic (Pyo18) and non-hemolytic E. coli strains (Pyo18
with deleted hlya-Pyo18ΔhlyA- and Pyo14) were compared. Following 4 h of
incubation, Pyo18 decreased epithelial cell numbers to 54%
(p < 0.001), and induced death of all stromal cells (p < 0.0001),
whereas Pyo18ΔhlyA and Pyo14 had no effect on cell numbers. Compared to
Pyo18ΔhlyA and Pyo14, respectively, Pyo18 induced a lower transcription
level of IL-1β (0.99 vs 152.0 vs 50.9 fold increase, p < 0.001), TNFα
(3.2 vs 49.9 vs 12.9 fold increase, p < 0.05) and IL-10 (0.4 vs 3.6
vs 2.6 fold increase, p < 0.001) in stromal cells, after 1 h of
incubation. This may be seen as an attempt of hemolytic E. coli to delay
the activation of the immune response. In conclusion, endometrial
epithelial and stromal cell damage induced by HlyA is a potential
relevant step of E. coli virulence in the pathogenesis of pyometra.