From Coxiella burnetii Infection to Pregnancy Complications: Key Role of the Immune Response of Placental Cells

Abstract

The infection of pregnant animals and women by Coxiella burnetii, an intracellular bacterium, compromises both maternal health and foetal development. The placenta is targeted by C. burnetii, as demonstrated by bacteriological and histological evidence. It now appears that placental strains of C. burnetii are highly virulent compared to reference strains and that placental injury involves different types of placental cells. Trophoblasts, the major placental cells, are largely infected by C. burnetii and may represent a replicating niche for the bacteria. The placenta also contains numerous immune cells, including macrophages, dendritic cells, and mast cells. Placental macrophages are infected and activated by C. burnetii in an unusual way of M1 polarisation associated with bacterial elimination. Placental mast cells eliminate bacteria through a mechanism including the release of extracellular actin filaments and antimicrobial peptides. In contrast, C. burnetii impairs the maturation of decidual dendritic cells, favouring bacterial pathogenicity. Our aim is to review C. burnetii infections of human placentas, paying special attention to both the action and function of the different cell types, immune cells, and trophoblasts targeted by C. burnetii in relation to foetal injury.

Keywords: Coxiella burnetii; dendritic cells; macrophages; mast cells; pregnancy; trophoblasts.

Figure 1

Placenta cell responses against C. burnetii infection. (A) Schematic representation of a full-term human placenta showing the maternal (decidua, myometrium) and foetal (intervillous space, chorion) parts. Placental cells are represented including extra-villous and villous trophoblasts and immune placental cells such as dendritic cells, macrophages (decidual and Hofbauer), and mast cells. During infection, C. burnetii was found in the placental tissue. (B) Ex vivo experiments based on in vitro infection of isolated primary cells from healthy at term human placentas reported the infectious capability of trophoblasts, dendritic cells, and macrophages by C. burnetii. In this context, although trophoblast infection leads to bacterial replication, the other cell lines present a specific anti-bacterial response promoting bacterial elimination. Thus, ex vivo experiments allow evaluating the level of C. burnetii infection at the placental level. Adapted from [42].