Infection and Persistence of Coxiella burnetii Clinical Isolate in the Placental Environment

Infection by Coxiella burnetii, the etiological agent of Q fever, poses the risk of causing severe obstetrical complications in pregnant women. C. burnetii is known for its placental tropism based on animal models of infection. The Nine Mile strain has been mostly used to study C. burnetii pathogenicity but the contribution of human isolates to C. burnetii pathogenicity is poorly understood. In this study, we compared five C. burnetii isolates from human placentas with C. burnetii strains including Nine Mile (NM) as reference. Comparative genomic analysis revealed that the Cb122 isolate was distinct from other placental isolates and the C. burnetii NM strain with a set of unique genes involved in energy generation and a type 1 secretion system. The infection of Balb/C mice with the Cb122 isolate showed higher virulence than that of NM or other placental isolates. We evaluated the pathogenicity of the Cb122 isolate by in vitro and ex vivo experiments. As C. burnetii is known to infect and survive within macrophages, we isolated monocytes and placental macrophages from healthy donors and infected them with the Cb122 isolate and the reference strain. We showed that bacteria from the Cb122 isolate were less internalized by monocyte-derived macrophages (MDM) than NM bacteria but the reference strain and the Cb122 isolate were similarly internalized by placental macrophages. The Cb122 isolate and the reference strain survived similarly in the two macrophage types. While the Cb122 isolate and the NM strain stimulated a poorly inflammatory program in MDM, they elicited an inflammatory program in placenta macrophages. We also reported that the Cb122 isolate and NM strain were internalized by trophoblastic cell lines and primary trophoblasts without specific replicative profiles. Placental explants were then infected with the Cb122 isolate and the NM strain. The bacteria from the Cb122 isolate were enriched in the chorionic villous foetal side. It is likely that the Cb122 isolate exhibited increased virulence in the multicellular environment provided by explants. Taken together, these results showed that the placental isolate of C. burnetii exhibits a specific infectious profile but its pathogenic role is not as high as the host immune response in pregnant women.

[1]  D. Raoult,et al.  Impact of Sex Hormones on Macrophage Responses to Coxiella burnetii , 2021, Frontiers in Immunology.

[2]  T. Démoulins,et al.  SARS-CoV-2 can infect and propagate in human placenta explants , 2021, Cell Reports Medicine.

[3]  D. Raoult,et al.  Sexual Dimorphism and Gender in Infectious Diseases , 2021, Frontiers in Immunology.

[4]  J. Mege,et al.  From Coxiella burnetii Infection to Pregnancy Complications: Key Role of the Immune Response of Placental Cells , 2021, Pathogens.

[5]  Yi Zhang,et al.  M2 macrophage‐derived G‐CSF promotes trophoblasts EMT, invasion and migration via activating PI3K/Akt/Erk1/2 pathway to mediate normal pregnancy , 2021, Journal of cellular and molecular medicine.

[6]  Anders Omsland,et al.  Selective Inhibition of Coxiella burnetii Replication by the Steroid Hormone Progesterone , 2020, Infection and Immunity.

[7]  D. Raoult,et al.  T-Bet Controls Susceptibility of Mice to Coxiella burnetii Infection , 2020, Frontiers in Microbiology.

[8]  N. Ghanem-Zoubi,et al.  Q fever during pregnancy: A narrative review. , 2020, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[9]  Daniel E. Voth,et al.  Coxiella burnetii: International pathogen of mystery. , 2020, Microbes and infection.

[10]  J. Mege,et al.  Full-Term Human Placental Macrophages Eliminate Coxiella burnetii Through an IFN-γ Autocrine Loop , 2019, Front. Microbiol..

[11]  Liping Jin,et al.  Dynamic Function and Composition Changes of Immune Cells During Normal and Pathological Pregnancy at the Maternal-Fetal Interface , 2019, Front. Immunol..

[12]  D. Raoult,et al.  The sexual dimorphism of anticardiolipin autoantibodies in acute Q fever patients. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[13]  J. Mege,et al.  A Fast and Reliable Method to Isolate Human Placental Macrophages , 2019, Current protocols in immunology.

[14]  M. Diamond,et al.  Zika virus–related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice , 2018, Science Translational Medicine.

[15]  C. Menge,et al.  Interaction of Coxiella burnetii Strains of Different Sources and Genotypes with Bovine and Human Monocyte-Derived Macrophages , 2018, Front. Cell. Infect. Microbiol..

[16]  L. Pereira,et al.  Congenital cytomegalovirus infection undermines early development and functions of the human placenta. , 2017, Placenta.

[17]  Bo Yu,et al.  CDD/SPARCLE: functional classification of proteins via subfamily domain architectures , 2016, Nucleic Acids Res..

[18]  D. Raoult,et al.  From Q Fever to Coxiella burnetii Infection: a Paradigm Change , 2016, Clinical Microbiology Reviews.

[19]  D. Raoult,et al.  Mouse Model of Coxiella burnetii Aerosolization , 2016, Infection and Immunity.

[20]  D. Raoult,et al.  Microbial culturomics unravels the halophilic microbiota repertoire of table salt: description of Gracilibacillus massiliensis sp. nov. , 2016, Microbial ecology in health and disease.

[21]  D. Raoult,et al.  Loss of TSS1 in hypervirulent Coxiella burnetii 175, the causative agent of Q fever in French Guiana. , 2015, Comparative immunology, microbiology and infectious diseases.

[22]  Andrew J. Page,et al.  Roary: rapid large-scale prokaryote pan genome analysis , 2015, bioRxiv.

[23]  Michael J E Sternberg,et al.  The Phyre2 web portal for protein modeling, prediction and analysis , 2015, Nature Protocols.

[24]  W. van der Hoek,et al.  Nationwide registry-based ecological analysis of Q fever incidence and pregnancy outcome during an outbreak in the Netherlands , 2015, BMJ Open.

[25]  D. Raoult,et al.  Reevaluation of the risk of fetal death and malformation after Q Fever. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  Torsten Seemann,et al.  Prokka: rapid prokaryotic genome annotation , 2014, Bioinform..

[27]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[28]  R. Kurten,et al.  Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages , 2013, Cellular microbiology.

[29]  A. García-Pérez,et al.  Evaluation of the efficacy of oxytetracycline treatment followed by vaccination against Q fever in a highly infected sheep flock. , 2013, Veterinary journal.

[30]  D. Raoult,et al.  Q fever and pregnancy: disease, prevention, and strain specificity , 2013, European Journal of Clinical Microbiology & Infectious Diseases.

[31]  A. Andersen,et al.  No excess risk of adverse pregnancy outcomes among women with serological markers of previous infection with Coxiella burnetii: evidence from the Danish National Birth Cohort , 2013, BMC Infectious Diseases.

[32]  J. Rebel,et al.  Q Fever in Pregnant Goats: Pathogenesis and Excretion of Coxiella burnetii , 2012, PloS one.

[33]  Sergey I. Nikolenko,et al.  SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing , 2012, J. Comput. Biol..

[34]  J. Mege,et al.  Coxiella burnetii, the Agent of Q Fever, Replicates within Trophoblasts and Induces a Unique Transcriptional Response , 2010, PloS one.

[35]  R. Heinzen,et al.  Coxiella burnetii Phase I and II Variants Replicate with Similar Kinetics in Degradative Phagolysosome-Like Compartments of Human Macrophages , 2010, Infection and Immunity.

[36]  Joshua S. Self,et al.  Presence of Coxiella burnetii DNA in the Environment of the United States, 2006 to 2008 , 2010, Applied and Environmental Microbiology.

[37]  Paramvir S. Dehal,et al.  FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments , 2010, PloS one.

[38]  Gajendra P. S. Raghava,et al.  Identification of ATP binding residues of a protein from its primary sequence , 2009, BMC Bioinformatics.

[39]  J. Samuel,et al.  Coxiella burnetii Isolates Cause Genogroup-Specific Virulence in Mouse and Guinea Pig Models of Acute Q Fever , 2009, Infection and Immunity.

[40]  A. Rodolakis.  Q Fever in Dairy Animals , 2009, Annals of the New York Academy of Sciences.

[41]  Alain Bernard,et al.  Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages , 2008, European journal of immunology.

[42]  M. Berri,et al.  Goats may experience reproductive failures and shed Coxiella burnetii at two successive parturitions after a Q fever infection. , 2007, Research in veterinary science.

[43]  D. Raoult,et al.  Natural history and pathophysiology of Q fever. , 2005, The Lancet. Infectious diseases.

[44]  D. Olive,et al.  Coxiella burnetii Avoids Macrophage Phagocytosis by Interfering with Spatial Distribution of Complement Receptor 31 , 2003, The Journal of Immunology.

[45]  D. Raoult,et al.  Q fever during pregnancy: diagnosis, treatment, and follow-up. , 2002, Archives of internal medicine.

[46]  D. Raoult,et al.  Interleukin-10 Stimulates Coxiella burnetiiReplication in Human Monocytes through Tumor Necrosis Factor Down-Modulation: Role in Microbicidal Defect of Q Fever , 2001, Infection and Immunity.

[47]  D. Raoult,et al.  Subversion of Monocyte Functions by Coxiella burnetii: Impairment of the Cross-Talk Between αvβ3 Integrin and CR3 , 1999, The Journal of Immunology.

[48]  D. Raoult,et al.  Q fever in pregnancy: case report after a 2-year follow-up. , 1998, The Journal of infection.

[49]  J. Mege,et al.  Immune response and Coxiella burnetii invasion. , 2012, Advances in experimental medicine and biology.

[50]  F Nistal de Paz,et al.  [Q fever]. , 1994, Medicina clinica.