Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner

T. G. A. M. Wolfs, S. G. Kallapur, C. L. Knox, G. Thuijls, I. Nitsos, G. R. Polglase, J. J. P. Collins, E. Kroon, J. Spierings, N. F. Shroyer, J. P. Newnham, A. H. Jobe, B. W. Kramer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.
Original languageEnglish
Pages (from-to)547-556
JournalMucosal Immunology
Volume6
Issue number3
DOIs
Publication statusPublished - May 2013

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