title: Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.
abstract: Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.
authors.affiliation: Center for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pilloux
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: LeRoy
authors.affiliation: Institute of Pathology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Brunel
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.affiliation: Center for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Greub
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002695:Chlamydiales / Q000502:physiology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D014709:Vero Cells