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Abstract
The intracellular bacterium Coxiella burnetii is responsible for Q fever, an infectious disease that increases the risk of abortion, preterm labor, and stillbirth in pregnant women. It has been shown that C. burnetii replicates in BeWo trophoblast cell line and inhibits the activation and maturation of decidual dendritic cells. Although tissue macrophages are known to be targeted by C. burnetii, no studies have investigated the interplay between placental macrophages and C. burnetii. Here, CD14+ macrophages from 46 full-term placentas were isolated by positive selection. They consisted of a mixed population of maternal and fetal origin as shown by genotype analysis. We showed that C. burnetii organisms infected placental macrophages after 4 h. When these infected macrophages were incubated for an additional 9-day culture, they completely eliminated organisms as shown by quantitative PCR. The ability of placental macrophages to form multinucleated giant cells was not affected by C. burnetii infection. The transcriptional immune response of placental macrophages to C. burnetii was investigated using quantitative real-time RT-PCR on 8 inflammatory and 10 immunoregulatory genes. C. burnetii clearly induced an inflammatory profile. Interestingly, the production by placental macrophages of interferon-γ, a cytokine known to be involved in efficient immune responses, was dramatically increased in response to C. burnetii. In addition, a clear correlation between interferon-γ production and C. burnetii elimination was found, suggesting that macrophages from full-term placentas eliminate C. burnetii under the control of an autocrine production of interferon-γ.
Highlights
The placenta is a unique chimeric organ made of fetal and maternal tissues at the materno-fetal interface
The phenotypic characterization of placental macrophages relies on the expression of CD68, a myeloid marker and CD14, a marker of circulating monocytes that is lacking in tissue macrophages other than placental macrophages (Ben Amara et al, 2013; Mezouar et al, 2019a)
These two populations are usually distinguished by their location within the placenta: Hofbauer cells are found in the fetal chorionic villi and decidual macrophages are found in decidua basalis (Pinhal-Enfield et al, 2012)
Summary
The placenta is a unique chimeric organ made of fetal (chorion) and maternal (decidua) tissues at the materno-fetal interface It is essential for nutritional exchanges and the immune tolerance of the fetus (Houser, 2012; Pinhal-Enfield et al, 2012). The role of placental macrophages in pregnancy is plural: they are involved in tissue remodeling, angiogenesis (Pongcharoen et al, 2007; Fong, 2008; Loegl et al, 2016), antigen presentation (Heikkinen et al, 2003, 2004), and maternal-fetal tolerance (Wang et al, 2018) They spontaneously form in vitro multinuclear giant cells (MGCs) even if the precise role of these MGCs remains to be elucidated (Ben Amara et al, 2013). Maintenance of the M2 polarization profile was observed (Joerink et al, 2011)
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