Frontiers in Immunology (Mar 2020)
Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses
- Cathelijne Heymans,
- Ilse H. de Lange,
- Ilse H. de Lange,
- Matthias C. Hütten,
- Matthias C. Hütten,
- Matthias C. Hütten,
- Matthias C. Hütten,
- Kaatje Lenaerts,
- Nadine J. E. de Ruijter,
- Lilian C. G. A. Kessels,
- Glenn Rademakers,
- Veerle Melotte,
- Werend Boesmans,
- Werend Boesmans,
- Masatoshi Saito,
- Masatoshi Saito,
- Haruo Usuda,
- Haruo Usuda,
- Sarah J. Stock,
- Owen B. Spiller,
- Michael L. Beeton,
- Matthew S. Payne,
- Boris W. Kramer,
- Boris W. Kramer,
- John P. Newnham,
- Alan H. Jobe,
- Alan H. Jobe,
- Matthew W. Kemp,
- Matthew W. Kemp,
- Matthew W. Kemp,
- Wim G. van Gemert,
- Wim G. van Gemert,
- Wim G. van Gemert,
- Tim G. A. M. Wolfs,
- Tim G. A. M. Wolfs
Affiliations
- Cathelijne Heymans
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
- Ilse H. de Lange
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
- Ilse H. de Lange
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Matthias C. Hütten
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Matthias C. Hütten
- Neonatology, Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands
- Matthias C. Hütten
- Neonatology, Department of Pediatrics, University Hospital Aachen, Aachen, Germany
- Matthias C. Hütten
- Neonatology, Department of Pediatrics, University Children's Hospital Würzburg, Würzburg, Germany
- Kaatje Lenaerts
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
- Nadine J. E. de Ruijter
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Lilian C. G. A. Kessels
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Glenn Rademakers
- Department of Pathology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, Netherlands
- Veerle Melotte
- Department of Pathology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, Netherlands
- Werend Boesmans
- Department of Pathology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, Netherlands
- Werend Boesmans
- Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Belgium
- Masatoshi Saito
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Masatoshi Saito
- Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
- Haruo Usuda
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Haruo Usuda
- Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
- Sarah J. Stock
- 0Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
- Owen B. Spiller
- 1Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
- Michael L. Beeton
- 2Cardiff School of Sport and Health Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom
- Matthew S. Payne
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Boris W. Kramer
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Boris W. Kramer
- Neonatology, Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands
- John P. Newnham
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Alan H. Jobe
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Alan H. Jobe
- 3Division of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States
- Matthew W. Kemp
- Division of Obstetrics and Gynecology, University of Western Australia, Perth, WA, Australia
- Matthew W. Kemp
- Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan
- Matthew W. Kemp
- 4School of Veterinary and Life Sciences, Murdoch University, Perth, WA, Australia
- Wim G. van Gemert
- Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
- Wim G. van Gemert
- 5Pediatric Surgery, Department of Surgery, Maastricht University Medical Center, Maastricht, Netherlands
- Wim G. van Gemert
- 6Department of Surgery, University Hospital Aachen, Aachen, Germany
- Tim G. A. M. Wolfs
- Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, Netherlands
- Tim G. A. M. Wolfs
- 7Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, Netherlands
- DOI
- https://doi.org/10.3389/fimmu.2020.00189
- Journal volume & issue
-
Vol. 11
Abstract
Background: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or chronic and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic, or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study was therefore to investigate the effect of acute, chronic, and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs.Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa, and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute), Ureaplasma parvum (UP) for 42 days (chronic), or repetitive microbial exposure (42 days UP with 2 or 7 days LPS).Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layers of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100β immunoreactivity, whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days.Conclusion: The in utero loss of PGP9.5 and S100β immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC.
Keywords
- Ureaplasma parvum
- intra-amniotic infection
- chorioamnionitis
- enteric nervous system
- sheep
- preterm birth
