Effects of Ureaplasma parvum lipoprotein multiple-banded antigen on pregnancy outcome in mice

Kaoru Uchida, Kumiko Nakahira, Kazuya Mimura, Takashi Shimizu, Francesco De Seta, Tetsu Wakimoto, Yasuhiro Kawai, Makoto Nomiyama, Koichi Kuwano, Secondo Guaschino, Itaru Yanagihara

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Abstract

Ureaplasma spp. are members of the family Mycoplasmataceae and have been considered to be associated with chorioamnionitis and preterm delivery. However, it is unclear whether Ureaplasma spp. have virulence factors related to these manifestations. The purpose of the present study was to determine whether the immunogenic protein multiple-banded antigen (MBA) from Ureaplasma parvum is a virulence factor for preterm delivery. We partially purified MBA from a type strain and clinical isolates of U. parvum, and also synthesized a diacylated lipopeptide derived from U. parvum, UPM-1. Using luciferase assays, both MBA-rich fraction MRF and UPM-1 activated the NF-κB pathway via TLR2. UPM-1 upregulated IL-1β, IL-6, IL-12p35, TNF-α, MIP2, LIX, and iNOS in mouse peritoneal macrophage. MRF or UPM-1 was injected into uteri on day 15 of gestation on pregnant C3H/HeN mice. The intrauterine MRF injection group had a significantly higher incidence of intrauterine fetal death (IUFD; 38.5%) than the control group (14.0%). Interestingly, intrauterine injection of UPM-1 caused preterm deliveries at high concentration (80.0%). In contrast, a low concentration of UPM-1 induced a significantly higher rate of fetal deaths (55.2%) than the control group (14.0%). The placentas of the UPM-1 injection group showed neutrophil infiltration and increased iNOS protein expression. Our data indicate that MBA from the clinical isolate of U. parvum is a potential virulence factor for IUFD and preterm delivery in mice and that the N-terminal diacylated lipopeptide is essential for the initiation of inflammation.

Original languageEnglish
Pages (from-to)118-127
Number of pages10
JournalJournal of Reproductive Immunology
Volume100
Issue number2
DOIs
Publication statusPublished - Dec 2013

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Keywords

  • Multiple-banded antigen
  • NF-κB
  • Preterm
  • Toll-like receptor 2
  • Ureaplasma parvum

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Uchida, K., Nakahira, K., Mimura, K., Shimizu, T., De Seta, F., Wakimoto, T., Kawai, Y., Nomiyama, M., Kuwano, K., Guaschino, S., & Yanagihara, I. (2013). Effects of Ureaplasma parvum lipoprotein multiple-banded antigen on pregnancy outcome in mice. Journal of Reproductive Immunology, 100(2), 118-127. https://doi.org/10.1016/j.jri.2013.10.001