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

Zarza, Sandra Madariaga; Mezouar, Soraya; Mège, Jean‐Louis

doi:10.3390/pathogens10050627

Cited by 12 publications

(11 citation statements)

References 77 publications

(107 reference statements)

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“…It was previously reported that many cell types, including myeloid cells [47,48], trophoblasts [4,49], lung cells [50,51], and adipocytes [5] dense circular structures, with diameters ranging from 250 nm to 700 nm dispersed in the cell cytoplasm, corresponding to the morphology and size of C. burnetii as previously described [54].…”

Section: Selection Of the Bewo Cell Line As An Appropriate Cellular M...mentioning

confidence: 76%

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Modulation of the E-cadherin in human cells infectedin vitrowithCoxiella burnetii

Osman

Mezouar

Belhaouari-Brahim

et al. 2022

Preprint

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High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells with C. burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C. burnetii. Moreover, the intracytoplasmic cell concentration of B-catenin (B-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/B-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/B-cat pathway were overexpressed in cells infected with C. burnetii. This was particularly evident with the highly virulent strain of C. burnetii, Guiana. Our data demonstrate that infection of BeWo cells by live C. burnetii modulates the E-cad/B-cat signaling pathway.

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Section: Selection Of the Bewo Cell Line As An Appropriate Cellular M...mentioning

confidence: 76%

“…It was previously reported that many cell types, including myeloid cells [47,48], trophoblasts [4,49], lung cells [50,51], and adipocytes [5] are susceptible to C. burnetii infection. To conduct our study, it was first necessary to select a cellular model with high expression of E-cad.…”

Section: Selection Of the Bewo Cell Line As An Appropriate Cellular M...mentioning

confidence: 99%

Modulation of the E-cadherin in human cells infectedin vitrowithCoxiella burnetii

Osman

Mezouar

Belhaouari-Brahim

et al. 2022

Preprint

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“…It was previously reported that many cell types, including myeloid cells [ 51 , 52 ], trophoblasts [ 4 , 53 ], lung cells [ 54 , 55 ], and adipocytes [ 5 ] are susceptible to C . burnetii infection.…”

Section: Resultsmentioning

confidence: 99%

Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii

et al. 2023

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High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii, the etiological agent of Q fever. Infection of BeWo cells with C. burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C. burnetii. Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected with C. burnetii. This was particularly evident with the highly virulent strain of C. burnetii, Guiana. Our data demonstrate that infection of BeWo cells by live C. burnetii modulates the E-cad/β-cat signaling pathway.

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“…They are mostly asymptomatic (60%), while 40% develop an acute Q fever and 2% progress to a persistent focal infection [ 1 ]. During pregnancy, exposure to C. burnetii increases the risk of developing acute Q fever but the illness is most often asymptomatic, which delays a diagnosis based on serology [ 2 , 3 , 4 , 5 , 6 ]. Hence, obstetrical complications including miscarriage, malformations, growth retardation, premature delivery and foetal death may occur [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…C. burnetii infects domestic ruminants, leading to infertility, endometritis and mastitis, and obstetrical complications such as still birth and abortion (90%) [ 12 , 13 ]. The pathogenesis of C. burnetii obstetrical complications in animal models results from placental infection and the recruitment of immune cells [ 2 , 3 , 13 , 14 ]. The role of C. burnetii organisms is counteracted by the benefits of antibiotic treatments and the vaccination strategy that have been proposed to reduce abortion rates [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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

Zarza

Militello

Gay

et al. 2023

IJMS

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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.

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

Cited by 12 publications

References 77 publications

Modulation of the E-cadherin in human cells infectedin vitrowithCoxiella burnetii

Modulation of the E-cadherin in human cells infectedin vitrowithCoxiella burnetii

Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii

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

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