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. 2023 Jan;89(1):e13650.
doi: 10.1111/aji.13650. Epub 2022 Nov 13.

Placentа of BCG-Vaccinated Women in early Pregnancy is Colonized with Non-Immunogenic Mycobacterial L-forms

Tanya Dimova  1 , Violeta Dimitrova  2 , Petar Grozdanov  3 , Nadya Markova  3
Affiliations

Placentа of BCG-Vaccinated Women in early Pregnancy is Colonized with Non-Immunogenic Mycobacterial L-forms

Tanya Dimova et al. Am J Reprod Immunol. 2023 Jan.

Abstract

Problem: Long-lived mycobacterial L-forms (mL-forms) could be detected in the blood of BCG-vaccinated people. We have previously found mL-forms in term placentas and blood of neonates, delivered by healthy BCG-vaccinated mothers as first formal demonstration that BCG vaccination in the childhood of the woman could affect her placentobiome during pregnancy. Of note, the isolated mL-forms reverted to the cell-walled state of the parental BCG bacilli in vitro.

Method of study: Here, we analyzed triple samples of blood, decidua and chorion taken from BCG-vaccinated pregnant women, directed to elective abortions (6-12 gestation weeks). The colonization of the primary samples with mycobacterial L-forms (mL-forms) was evaluated using microbiological isolation and subsequent identification by real time PCR and morphological characterization by light microscopy and SEM. The potential of early placenta-derived mL-forms to expand mycobacteria-reactive γδ T cells in vitro was assessed using FACS, whereas their immunogenicity in vivo was followed up after i.p. inoculation in rats.

Results: Our results showed two important findings: 1) viable filterable mL-forms varying in size, shape and proliferation modes are capable of colonizing the gestational tissues of BCG-vaccinated women early in pregnancy and 2) early placenta-derived mL-forms are not as immunogenic as walled M. bovis BCG bacilli, shown by lack of stimulation of mycobacteria-reactive γδ T cells co-cultured with early placenta-derived mL-forms and inefficient internalization of mL-forms by rat's peritoneal phagocytes in vivo.

Conclusion: Although generally thought to be reduced in virulence, mL-forms could provide a reservoir, hidden from the immune system especially in an immune privileged niche like placenta.

Keywords: BCG vaccination; human pregnancy; immunogenicity; mycobacterial L-forms.

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References

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