Characterization of Early Stages of Human Alveolar Infection by the Q Fever Agent Coxiella burnetii

Human Q fever is caused by the intracellular bacterial pathogen Coxiella burnetii. Q fever presents with acute flu-like and pulmonary symptoms or can progress to chronic, severe endocarditis. After human inhalation, C. burnetii is engulfed by alveolar macrophages and transits through the phagolysosomal maturation pathway, resisting the acidic pH of lysosomes to form a parasitophorous vacuole (PV) in which to replicate. Previous studies showed that C. burnetii replicates efficiently in primary human alveolar macrophages (hAMs) in ex vivo human lung tissue. Although C. burnetii replicates in most cell types in vitro, the pathogen does not grow in non-hAM cells of human lung tissue. In this study, we investigated the interaction between C. burnetii and other pulmonary cell types apart from the lung environment. C. burnetii formed a prototypical PV and replicated efficiently in human pulmonary fibroblasts and in airway, but not alveolar, epithelial cells. Atypical PV expansion in alveolar epithelial cells was attributed in part to defective recruitment of autophagy-related proteins. Further assessment of the C. burnetii growth niche showed that macrophages mounted a robust interleukin 8 (IL-8), neutrophil-attracting response to C. burnetii and ultimately shifted to an M2-polarized phenotype characteristic of anti-inflammatory macrophages. Considering our findings together, this study provides further clarity on the unique C. burnetii-lung dynamic during early stages of human acute Q fever.