title: Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep.
abstract: The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different proinflammatory mediators, we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic (IA) injections of media (control) or Ureaplasma parvum serovar 3 either 7 or 70 d before preterm delivery. Another group received an IA injection of Escherichia coli LPS 2 d prior to delivery. To test for interactions, IA U. parvum-exposed animals were challenged with IA LPS and delivered 2 d later. All animals were delivered at 124 ± 1-d gestation (term = 150 d). Compared with the 2-d LPS exposure group, the U. parvum 70 d + LPS group had 1) decreased lung pro- and anti-inflammatory cytokine expression and 2) fewer CD3(+) T lymphocytes, CCL2(+), myeloperoxidase(+), and PU.1(+) cells in the lung. Interestingly, exposure to U. parvum for 7 d did not change responses to a subsequent IA LPS challenge, and exposure to IA U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGF-β1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70 d + LPS but not U. parvum 7 d + LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of downregulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis-exposed preterm infants may respond to lung injury and postnatal nosocomial infections.
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA. suhas.kallapur@cchmc.org
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Christine L
authors.initials: CL
authors.lastname: Knox
authors.forename: Clare A
authors.initials: CA
authors.lastname: Berry
authors.forename: Jennifer J P
authors.initials: JJ
authors.lastname: Collins
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.forename: Noah H
authors.initials: NH
authors.lastname: Hillman
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Claire
authors.initials: C
authors.lastname: Chougnet
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002821:Chorioamnionitis / Q000276:immunology; D003428:Cross Infection / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005333:Fetus; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D011014:Pneumonia / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D034561:Sheep, Domestic; D014509:Ureaplasma; D016869:Ureaplasma Infections / Q000150:complications / Q000276:immunology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides