Severe pneumonia due to Parachlamydia acanthamoebae following intranasal inoculation: a mice model
Ludovic Pilloux1, Nicola Casson1, Kirsten Sommer2
1Centre for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Abstract:
Parachlamydia acanthamoebae is an obligate intracellular bacterium naturally infecting free-living amoebae. The role of this bacterium as an agent of pneumonia is suggested by sero-epidemiological studies and molecular surveys. Furthermore, P. acanthamoebae may escape macrophages microbicidal effectors. Recently, we demonstrated that intratracheal inoculation of P. acanthamoebae induced pneumonia in 100% of infected mice. However, the intratracheal route of infection is not the natural way of infection and we therefore developed an intranasal murine model. Mice inoculated with P. acanthamoebae by intranasal inoculation lost 18% of their weight up to 8 days post-inoculation. All mice presented histological signs of pneumonia at day 2, 4, 7, and 10 post-inoculation, whereas no control mice harboured signs of pneumonia. A 5-fold increase in bacterial load was observed from day 0 to day 4 post-inoculation. Lungs of inoculated mice were positive by Parachlamydia-specific immunohistochemistry 4 days post-inoculation, and P. acanthamoebae were localized within macrophages. Thus, we demonstrated that P. acanthamoebae induce a severe pneumonia in mice. This animal model (i) further supports the role of P. acanthamoebae as an agent of pneumonia, confirming the third Koch postulate, and (ii) identified alveolar macrophages as one of the initial cells where P. acanthamoebae is localized following infection.
Insights
Parachlamydia acanthamoebae causes severe pneumonia in mice via intranasal infection. This new model confirms its role as a pneumonia agent and identifies alveolar macrophages as key infection sites.
Area of Science:
- Microbiology
- Infectious Diseases
- Pulmonology
Background:
- Parachlamydia acanthamoebae, an obligate intracellular bacterium, is found in free-living amoebae.
- Previous studies suggested its potential role in pneumonia and ability to evade macrophage defenses.
- Intratracheal inoculation in mice previously induced pneumonia, but this is not a natural infection route.
Purpose of the Study:
- To develop and validate an intranasal murine model for studying Parachlamydia acanthamoebae-induced pneumonia.
- To confirm the role of P. acanthamoebae as a causative agent of pneumonia using Koch's postulates.
- To identify the initial host cells involved in P. acanthamoebae respiratory infections.
Main Methods:
- Development of an intranasal inoculation model in mice using P. acanthamoebae.
- Monitoring of weight loss, histological signs of pneumonia, and bacterial load post-inoculation.
- Immunohistochemical analysis to detect bacterial presence and localization in lung tissues.
Main Results:
- Intranasal inoculation led to significant weight loss (18%) and histological evidence of pneumonia in all infected mice.
- Bacterial load in the lungs increased 5-fold from day 0 to day 4 post-inoculation.
- P. acanthamoebae was detected in lung tissues via immunohistochemistry by day 4 and was localized within alveolar macrophages.
Conclusions:
- The intranasal murine model effectively replicates P. acanthamoebae-induced pneumonia, supporting its role as a pneumonia agent.
- This study fulfills Koch's third postulate, establishing a causal link between P. acanthamoebae and pneumonia.
- Alveolar macrophages are identified as primary host cells for P. acanthamoebae during respiratory infection.
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