Mother-to-newborn transmission of mycobacterial L-forms and V\u03b42 T-cell response in placentobiome of BCG-vaccinated pregnant women

T Dimova,V Dimitrova,A Nikolov,L Djerov,A Terzieva,P Grozdanov,N Markova

doi:10.1038/s41598-017-17644-z

Abstract

The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L bacterial forms are extremely scarce. Bacille Calmette-Guérin is an attenuated strain of M. bovis and the only licensed vaccine used for tuberculosis prevention. We already have shown that filterable L-forms of BCG exist freely in the vaccine and are able to reproduce and to form colonies. The present study was focused on the placental microbiome in the context of mother’s BCG vaccination. Here we report an isolation of filterable mycobacterial L-form cultures from gestational tissues and blood of healthy newborns delivered by healthy BCG-vaccinated mothers after normal pregnancy. Of note, vertically transmitted mycobacterial L-forms as a part of placentobiome of the pregnant women didn’t influence the number of resident pathogen-reactive Vδ2 cells. Placenta colonization with mycobacterial L-forms occurs by maternal blood-to-decidua transfer very early in gestation. Together, these data showed that BCG L-forms have the capacity to pass trans-placental barrier and that maternal BCG vaccination affects the placentobiome.

Highlights

Randomized controlled trials have shown efficacies ranging from 0 to 80%13–15
Having in mind all unusual properties of L-forms and their long-lasting persistence in vivo[4,33,34] and the presence of viable filterable L-form elements in commercial BCG vaccine capable of colonizing the newborns[11], we aimed to investigate whether the placentobiome of BCG-vaccinated healthy pregnant women contains mycobacterial L-forms able to enter neonate’s circulation and what would be their effect on the amount of placental pathogen-reactive Vδ2 γδ T cells
The present study is focused on the placental microbiome - new and hot topic of research - in the context of mother’s BCG vaccination

Summary

Introduction

Randomized controlled trials have shown efficacies ranging from 0 to 80%13–15. the BCG is the only licensed vaccine used for tuberculosis (TB) prevention. A growing body of data provides convincing evidence that both mycobacterial infection and BCG vaccination induce a specific expansion and phenotype of Vδ2 γδ T cells in vivo[18,19,20,21] and in vitro during re-stimulation with mycobacterial lysates and BCG22. Vδ2 T cells typically comprise 5% of total T cells in adult human blood, this population can expand rapidly in response to a wide range of pathogens and is thought to play a key role in human antimicrobial immunity[24,25,26,27]. Many bacteria including MbT and BCG produce natural non-peptide low molecular weight phosphorylated metabolites (so called phosphoantigens) which induce Vδ2-cell expansion[19]. The immune system of mid-gestation fetus contains effector, phosphoantigens-reactive Vδ2 cells with cytotoxic activity and Th1 cytokine profile[31]. How early during pregnancy and the possible pathway for L-forms placenta colonization were examined in this study

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Conclusion