Murine alveolar macrophages are highly susceptible to replication of Coxiella burnetii phase II In Vitro

Abstract

Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs, C. burnetii infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection in vitro. In the study described here, we investigated and characterized the infection of primary murine AMs by C. burnetii phase II in vitro. Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to C. burnetii multiplication in vitro. Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of C. burnetii replication, we performed experiments with AMs from Nos2-/- or Ifng-/- mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from Il4-/- mice were more restrictive to C. burnetii replication, supporting the importance of M2 polarization for the permissiveness of AMs to C. burnetii replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of C. burnetii growth in primary macrophages.