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Accueil > Recherche > Gynécologie & obstétrique > David Baud Lab

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David Baud Lab

Pr David BaudDavid Baud, MD-PhD, PD
Chief of service of obstetrics

Tel. +41 21 314 3953
Mobile: +41 79 556 1351
Contact mail

                                                   

Research Topics

WADDLIA CHONDROPHILA, AN EMERGING AGENT OF ADVERSE PREGNANCY OUTCOMES IN HUMAN

 

Approximately 25% of women will experience at least one miscarriage during their life. Despite a large number of possible investigations, a cause of the miscarriage is identified in less than 50% of the cases. Intracellular bacteria, which are not routinely investigated in clinical practice, might represent possible agents of miscarriages of unknown etiology. Listeria monocytogenes, Chlamydia trachomatis and Coxiella burnetii are known intracellular bacteria associated with adverse pregnancy outcome. Recently, several studies identified Waddlia chondrophila, an emerging intracellular bacterium belonging to the order of Chlamydiales, to be strongly associated with adverse pregnancy outcomes both in women and animals. Waddlia positive serologies as well as PCR and immunohistochemistry (both in the genital tract and placenta) were more likely to be present in women with miscarriages.

 

We recently developed a mouse genital model of infection showing that W. chondrophila is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed immune response. This new animal model will be used in the future to further explore the pathology induced by W. chondrophila. Three main topics are currently investigated using this animal model

  • Inter-animal transmission of W. chondrophila;

  • Impact on pregnancies;

  • Immunology during pregnancy (in comparison with human studies presented below).

 


Figure: Detection of W.chondrophila by immunofluorescence in a spleen section at day14 post-infection. Co-visualization of mouse cells by DAPI (nuclei in blue) and bacteria (green) by a specific anti-W.chondrophila antibody (200X magnification).


IMMUNOLOGY OF WADDLIA CHONDROPHILA

 

Despite the strong evidences of the role of W. chondrophila in adverse pregnancy outcomes, nothing is known regarding the mode of infection, the effect on the neonate and the pathophysiology of this emerging bacterium. In addition, there is no available literature on the induced immune response by W. chondrophila in humans and the effect of W. chondrophila on the mechanisms behind these responses.

Our group aims to fulfil these current knowledge gaps on the immune responses against W. chondrophila, the mode of infection, and the effect on the fetus/neonate. Three main topics are currently studied:

  • The mode of infection of W. chondrophila infection during pregnancy;

  • The immune response against W. chondrophila in women who experienced miscarriage compared to women with uneventful pregnancies;

  • The immunological mechanisms related to W. chondrophila induced miscarriage.


WADDLIA CHONDROPHILA INFECTION IN MEN

 

As most of the studies on genital intracellular pathogens focused mainly on women and female animal models, little is known about the pathogenic role of these bacteria in men. Since other intracellular bacteria have been associated with male infertility, we are further characterizing the impact of W. chondrophila on male fertility by developing

  • A male animal model of infection,

  • An in vitro model of infection of spermatozoa and

  • By investigating couple suffering from recurrent miscarriages and infertility for evidence of  W. chondrophila infection.

Moreover, other cause of failed fertility treatment are investigated through the sperm microbiota.

 

Figure: Human spermatozoa infected with W. chondrophila. Human spermatozoa stained with concanavaline A-rhodamine (red) and DAPI (nuclei, blue) and co-visualization of bacteria stained (green) with a specific anti-W.chondrophila antibody (400X magnification).


VACCINE AGAINST CHLAMYDIA TRACHOMATIS

 

C. trachomatis is the most commonly reported sexually transmitted bacterial infection worldwide, with more than 100 million new cases annually, 90% being asymptomatic. However, infection may translate into significant complications such as miscarriage, preterm birth, neonatal pneumonia, tubal infertility, ectopic pregnancy, pelvic inflammatory disease (PID), blindness and urethritis. Screening and prevention strategies have failed to slow down the current epidemics. Vaccination would be more effective than other intervention in controlling ongoing epidemics of C. trachomatis. Even though various strategies using live bacteria, inactivated bacteria, subunit antigenic determinants, recombinant proteins and plasmid DNA have been implemented, a human C. trachomatis vaccine has been elusive.

 

The aim of this ongoing research is to obtain proof of principle of a safe and efficient Salmonella-based vaccine against C. trachomatis. The use of live attenuated Salmonella to deliver recombinant chlamydial antigens to the immune system is an attractive strategy, because Salmonella:

  • Predominantly induces Th1-biased immunity which is effective for suppressing intracellular pathogens,

  • Achieves long lasting mucosal, humoral and cellular immunity against their heterologous antigens,

  • Is cheap to produce,

  • Does not require cold-chain preservation,

  • Is a needle free oral or mucosal immunization tool and,

  • Protects also against typhoid fever.

This is of major importance because a chlamydia vaccine should be also accessible to developing countries. Moreover, vaccine construction based on a licensed vaccine vector such as Ty21a may fundamentally expedite vaccine development.

 

Figure: Human macrophage infected with attenuated Salmonella expressing GFP (green) only under stress condition (selective “in vivo” but not “in vitro” condition). Macrophage stained with concanavaline A-rhodamine (red9 and DAPI (nuclei, blue).