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 poible role ofW. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability ofW. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering thatW. 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 ofW. chondrophila. Following intranasal inoculation of 2 x 108W. 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 aociated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was aociated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role ofW. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.