Parachlamydia acanthamoebae as a respiratory pathogen: Challenge dose titration in a bovine model

Background : The majority of community acquired pneumonia (CAP) in humans fails to be diagnosed aetiologically. Besides Chlamydia spp., Chlamydia -like organisms are thought to be causative in CAP. Pneumopathogenic potential has been described for Parachlamydia ( P. ) acanthamoebae , a well studied agent among the Chlamydia -like organisms. Objective : This study aimed to evaluate the pathogenicity of Parachlamydia ( P. ) acanthamoebae as a potential agent of lower respiratory tract disease. A bovine model of induced lung infection was introduced for translational reasons. Method : Intrabronchial inoculation with P. acanthamoebae was performed in healthy calves aged 2-3 months (n=30) using two different challenge doses: 10 8 and 10 10 inclusion-forming units (ifu) per animal. Controls received heat inactivated pathogen. Results : While the challenge with 10 8 ifu of viable Parachlamydia resulted in a mild degree of clinical illness, the dose of 10 10 ifu induced a respiratory desease that became clinically apparent 1-2 days after challenge. Parachlamydiae were detected in neutrophils and alveolar macrophages within pulmonary lesions by immunohistochemistry. This was in accordance with molecularbiological findings as well as with re-isolation of Parachlamydia . Clinical outcome, acute phase reactants, pathological findings and antigen load exhibited an initial dose-dependent effect of severity. Conclusion : The bovine lung was shown to be susceptible for P. acanthamoebae. Recommending the challenge dose of 10 10 ifu, this large animal model is suitable to elucidate host-pathogen interactions.