title: Coxiella burnetii, the agent of Q fever, replicates within trophoblasts and induces a unique transcriptional response.
abstract: Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium typically found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle and can undergo chronic evolution in a minority of pregnant women. Because C. burnetii is found in the placentas of aborted fetuses, we investigated the possibility that it could infect trophoblasts. Here, we show that C. burnetii infected and replicated in BeWo trophoblasts within phagolysosomes. Using pangenomic microarrays, we found that C. burnetii induced a specific transcriptomic program. This program was associated with the modulation of inflammatory responses that were shared with inflammatory agonists, such as TNF, and more specific responses involving genes related to pregnancy development, including EGR-1 and NDGR1. In addition, C. burnetii stimulated gene networks organized around the IL-6 and IL-13 pathways, which both modulate STAT3. Taken together, these results revealed that trophoblasts represent a protective niche for C. burnetii. The activation program induced by C. burnetii in trophoblasts may allow bacterial replication but seems unable to interfere with the development of normal pregnancy. Such pathophysiologocal processes should require the activation of immune placental cells associated with trophoblasts.
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, CNRS-IRD UMR 6236, IFR 48, Université de la Méditerranée, Marseille, France.
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Priol
authors.forename: Catherine
authors.initials: C
authors.lastname: Lépolard
authors.forename: Suzana P
authors.initials: SP
authors.lastname: Salcedo
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.forename: Florence
authors.initials: F
authors.lastname: Bretelle
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000818:Animals; D016997:Coxiella burnetii / Q000378:metabolism / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D020869:Gene Expression Profiling; D007249:Inflammation; D018793:Interleukin-13 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010588:Phagosomes / Q000382:microbiology; D010641:Phenotype; D011778:Q Fever / Q000382:microbiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000382:microbiology*
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D018793:Interleukin-13; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse