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Perinatal Listeria monocytogenes susceptibility despite preconceptual priming and maintenance of pathogen-specific CD8+ T cells during pregnancy

Abstract

Listeria monocytogenes (Lm) is an intracellular bacterium with unique predisposition for systemic maternal infection during pregnancy and morbid consequences for the developing fetus. Given the high mortality associated with prenatal Lm infection, strategies for augmenting protective immunity during the exceedingly vulnerable period of pregnancy are urgently needed. Herein, protection conferred by attenuated Lm administered before pregnancy against subsequent virulent Lm prenatal infection was evaluated. We show that protection against secondary Lm infection in non-pregnant mice is sharply moderated during allogeneic pregnancy because significantly more bacteria are recovered from maternal tissues, despite the numerical and functional preservation of pathogen-specific CD8+ T cells. More importantly, preconceptual priming does not protect against in utero invasion or fetal wastage because mice inoculated with attenuated Lm prior to pregnancy and naive pregnant controls each showed near complete fetal resorption and pathogen recovery from individual concepti after Lm infection during pregnancy. Remarkably, the lack of protection against prenatal Lm infection with preconceptual priming in allogeneic pregnancy is restored during syngeneic pregnancy. Thus, maternal–fetal antigen discordance dictates the ineffectiveness of preconceptual vaccination against fetal complications after prenatal Lm infection, despite the numerical and functional preservation of pathogen-specific CD8+ T cells.

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Acknowledgements

We thank Dr Ashley Sherrid and Dr Tobias Kollmann (University of British Columbia) for helpful discussions, and the NIH tetramer core facility (Atlanta, GA, USA) for providing mouse H-2K tetramers.. This work is supported, in part, by the NIAID through awards R01AI087830, R01AI100934 and R21AI112186. SSW holds an Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund.

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Clark, D., Chaturvedi, V., Kinder, J. et al. Perinatal Listeria monocytogenes susceptibility despite preconceptual priming and maintenance of pathogen-specific CD8+ T cells during pregnancy. Cell Mol Immunol 11, 595–605 (2014). https://doi.org/10.1038/cmi.2014.84

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