Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis (original) (raw)

Nature volume 455, pages 1114–1118 (2008)Cite this article

Abstract

The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism1. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB2. However, their respective species specificity has complicated investigations on their in vivo role3,4. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.

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Data deposits

The Gerbil Ecad and Gerbil Met nucleotide sequences are deposited in GenBank under accession numbers EU878370 and EU878371, respectively.

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Acknowledgements

This paper is dedicated to the memory of Charles Babinet, our friend and colleague, who died a few days before the submission of this manuscript. We thank his collaborators S. Vandormael-Pournin, C. Kress and M. Cohen-Tannoudji, as well as L. Larue and S. Tajbakhsh for help in generating the knock-in mice. We thank C. Hill for the gift of the pPL2_lux_-P hlyA plasmid, M.-A. Nahori for help with animal experiments, P. Roux for help with confocal imaging, P.-M. Lledo and M. Gabellec for help with vibratome sectioning, V. Masse for help with statistical analysis and O. Lortholary for his support. We also thank S. Mostowy for reading the paper. This work received financial support from the Institut Pasteur, Inserm and INRA. O. Disson received financial support from the Fondation pour la Recherche Médicale (FRM) and Inserm, P.C. is an Howard Hughes Medical Institute international research scholar and M.L. is a recipient of an Inserm interface contract.

Author Contributions M.L. planned the project and analysed the experiments, together with P.C., as well as O. Disson, S.G., E.H. and G.N. O. Disson, S.G., E.H. and G.N. performed the experiments. Engineering of knock-in mice was done with F.L.-V. and C.B. O. Dussurget was involved in bioluminescence imaging; M.R. and A.L.M. were involved in the epidemiological study. M.L. wrote the manuscript and all co-authors commented on it.

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Author notes

  1. Olivier Disson, Solène Grayo and Eugénie Huillet: These authors contributed equally to this work.
  2. Charles Babinet: Deceased.

Authors and Affiliations

  1. Institut Pasteur, Groupe Microorganismes et Barrières de l’Hôte, Unité des Interactions Bactéries-Cellules, F-75015 Paris, France
    Olivier Disson, Solène Grayo, Georgios Nikitas & Marc Lecuit
  2. Inserm Avenir U604, F-75015 Paris, France
    Olivier Disson, Solène Grayo, Georgios Nikitas & Marc Lecuit
  3. Institut Pasteur, Centre National de Référence des Listeria, F-75015 Paris, France
    Solène Grayo, Marie Ragon, Alban Le Monnier & Marc Lecuit
  4. Institut Pasteur, Unité des Interactions Bactéries-Cellules, F-75015 Paris, France
    Eugénie Huillet, Olivier Dussurget & Pascale Cossart
  5. Inserm U604, F-75015 Paris, France
    Eugénie Huillet, Olivier Dussurget & Pascale Cossart
  6. INRA USC2020, F-75015 Paris, France
    Eugénie Huillet, Olivier Dussurget & Pascale Cossart
  7. Institut Pasteur, Centre d’Ingénierie Génétique Murine, F-75015 Paris, France
    Francina Langa-Vives
  8. Institut Pasteur, Unité de Biologie du Développement, F-75015 Paris, France
    Charles Babinet
  9. Centre d’Infectiologie Necker-Pasteur, Service des Maladies Infectieuses et Tropicales, Hôpital Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, F-75015 Paris, France
    Marc Lecuit

Authors

  1. Olivier Disson
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  2. Solène Grayo
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  3. Eugénie Huillet
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  4. Georgios Nikitas
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  5. Francina Langa-Vives
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  6. Olivier Dussurget
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  7. Marie Ragon
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  8. Alban Le Monnier
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  9. Charles Babinet
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  10. Pascale Cossart
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  11. Marc Lecuit
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Corresponding author

Correspondence toMarc Lecuit.

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Disson, O., Grayo, S., Huillet, E. et al. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis.Nature 455, 1114–1118 (2008). https://doi.org/10.1038/nature07303

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Editorial Summary

Crossing the placental barrier

Listeriosis and other microbial infections in pregnancy can affect the fetus as well as the mother, but little is known about how pathogens cross the placental barrier. Disson et al. investigated the process using two complementary animal models infected by Listeria monocytogenes. They show that two virulence factors or invasion proteins, InlA and InlB, are required for the transfer of pathogen to the placenta. Thus by blocking one or both of these pathways it may be possible to stop microbes passing into the fetus. Conversely, it may be possible to exploit these pathways to target therapeutic molecules across the same barrier.