title: Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection.
abstract: Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.
authors.affiliation: Materno-fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, Maternity, University Hospital Lausanne, Switzerland.
authors.forename: Sam
authors.initials: S
authors.lastname: Vasilevsky
authors.affiliation: Materno-fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, Maternity, University Hospital Lausanne, Switzerland.
authors.forename: Joel
authors.initials: J
authors.lastname: Gyger
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale Lausanne Lausanne, Switzerland ; Institute of Animal Pathology, University of Bern Bern, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piersigilli
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Institute of Microbiology, University Hospital Lausanne, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pilloux
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Institute of Microbiology, University Hospital Lausanne, Switzerland.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Greub
authors.affiliation: Materno-fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, Maternity, University Hospital Lausanne, Switzerland.
authors.forename: Milos
authors.initials: M
authors.lastname: Stojanov
authors.affiliation: Materno-fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, Maternity, University Hospital Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Baud
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002695:Chlamydiales / Q000502:physiology*; D004195:Disease Models, Animal; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology* / Q000473:pathology*; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D060737:Reproductive Tract Infections / Q000382:microbiology* / Q000473:pathology*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G
keywords: Chlamydia-like; adverse pregnancy outcome; genital tract infection; intracellular bacteria; zoonosis