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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Mylonakis, E., Paliou, M., Hohmann, E. L., Calderwood, S. B. & Wing, E. J. Listeriosis during pregnancy: a case series and review of 222 cases. Medicine (Baltimore) 81, 260–269 (2002)
Hamon, M., Bierne, H. & Cossart, P. Listeria monocytogenes: a multifaceted model. Nature Rev. Microbiol. 4, 423–434 (2006)
Lecuit, M. et al. A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes . EMBO J. 18, 3956–3963 (1999)
Khelef, N., Lecuit, M., Bierne, H. & Cossart, P. Species specificity of the Listeria monocytogenes InlB protein. Cell. Microbiol. 8, 457–470 (2006)
Lecuit, M. Human listeriosis and animal models. Microbes Infect. 9, 1216–1225 (2007)
Abram, M. et al. Murine model of pregnancy-associated Listeria monocytogenes infection. FEMS Immunol. Med. Microbiol. 35, 177–182 (2003)
Cossart, P., Pizarro-Cerda, J. & Lecuit, M. Invasion of mammalian cells by Listeria monocytogenes: functional mimicry to subvert cellular functions. Trends Cell Biol. 13, 23–31 (2003)
Pizarro-Cerda, J. & Cossart, P. Bacterial adhesion and entry into host cells. Cell 124, 715–727 (2006)
Mengaud, J., Ohayon, H., Gounon, P., Mege, R. M. & Cossart, P. E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 84, 923–932 (1996)
Shen, Y., Naujokas, M., Park, M. & Ireton, K. InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell 103, 501–510 (2000)
Braun, L., Ghebrehiwet, B. & Cossart, P. gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes . EMBO J. 19, 1458–1466 (2000)
Jonquieres, R., Pizarro-Cerda, J. & Cossart, P. Synergy between the N- and C-terminal domains of InlB for efficient invasion of non-phagocytic cells by Listeria monocytogenes . Mol. Microbiol. 42, 955–965 (2001)
Lecuit, M. et al. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292, 1722–1725 (2001)
Jacquet, C. et al. A molecular marker for evaluating the pathogenic potential of foodborne Listeria monocytogenes . J. Infect. Dis. 189, 2094–2100 (2004)
Lecuit, M. et al. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin. Proc. Natl Acad. Sci. USA 101, 6152–6157 (2004)
Bakardjiev, A. I., Stacy, B. A., Fisher, S. J. & Portnoy, D. A. Listeriosis in the pregnant guinea pig: a model of vertical transmission. Infect. Immun. 72, 489–497 (2004)
Le Monnier, A. et al. ActA is required for crossing of the fetoplacental barrier by Listeria monocytogenes . Infect. Immun. 75, 950–957 (2007)
Pirie, J. H. H. A new disease of veld rodents. ‘Tiger river disease’. Publ. S. Afr. Inst. Med. Res. 3, 163–186 (1927)
Schubert, W. D. et al. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell 111, 825–836 (2002)
Niemann, H. H. et al. Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. Cell 130, 235–246 (2007)
Lecuit, M. & Cossart, P. Genetically-modified-animal models for human infections: the Listeria paradigm. Trends Mol. Med. 8, 537–542 (2002)
Glaser, P. et al. Comparative genomics of Listeria species. Science 294, 849–852 (2001)
Vazquez-Boland, J. A. et al. Listeria pathogenesis and molecular virulence determinants. Clin. Microbiol. Rev. 14, 584–640 (2001)
Lecuit, M., Ohayon, H., Braun, L., Mengaud, J. & Cossart, P. Internalin of Listeria monocytogenes with an intact leucine-rich repeat region is sufficient to promote internalization. Infect. Immun. 65, 5309–5319 (1997)
Braun, L., Ohayon, H. & Cossart, P. The InIB protein of Listeria monocytogenes is sufficient to promote entry into mammalian cells. Mol. Microbiol. 27, 1077–1087 (1998)
Rubin, L. L. et al. A cell culture model of the blood–brain barrier. J. Cell Biol. 115, 1725–1735 (1991)
Bierne, H. & Cossart, P. InlB, a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J. Cell Sci. 115, 3357–3367 (2002)
Athman, R. et al. Shigella flexneri infection is dependent on villin in the mouse intestine and in primary cultures of intestinal epithelial cells. Cell. Microbiol. 7, 1109–1116 (2005)
Dramsi, S., Levi, S., Triller, A. & Cossart, P. Entry of Listeria monocytogenes into neurons occurs by cell-to-cell spread: an in vitro study. Infect. Immun. 66, 4461–4468 (1998)
Perez-Garcia, C. C. et al. A simple procedure to perform intravenous injections in the Mongolian gerbil (Meriones unguiculatus). Lab. Anim. 37, 68–71 (2003)
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 pPL2lux-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.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Information
This file contains Supplementary Methods with Tables 1 and 2, References for Supplementary Methods, Supplementary Figures 1-10 with Legends. Supplementary Table 1 with Legend and Supplementary Movies Legends 1 and 2 (PDF 4198 kb)
Supplementary Movie 1
This file contains Supplementary Movie 1 (MOV 16375 kb)
Supplementary Movie 2
This file contains Supplementary Movie 2 (MOV 12781 kb)
Supplementary Movie 3
This file contains Supplementary Movie 3 (MOV 14209 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature07303
This article is cited by
-
Infections at the maternal–fetal interface: an overview of pathogenesis and defence
Nature Reviews Microbiology (2022)
-
Bacterial inhibition of Fas-mediated killing promotes neuroinvasion and persistence
Nature (2022)
-
Maternal natural killer cells at the intersection between reproduction and mucosal immunity
Mucosal Immunology (2021)
-
Emerging technologies and infection models in cellular microbiology
Nature Communications (2021)
-
Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST
Scientific Reports (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.