Invasive Extravillous Trophoblasts Restrict Intracellular Growth and Spread of Listeria monocytogenes

被引:71
作者
Zeldovich, Varvara B. [1 ,2 ,3 ]
Robbins, Jennifer R. [1 ,2 ,4 ]
Kapidzic, Mirhan [5 ]
Lauer, Peter [6 ]
Bakardjiev, Anna I. [1 ,2 ,3 ]
机构
[1] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA
[4] Xavier Univ, Dept Biol, Cincinnati, OH 45207 USA
[5] Univ Calif San Francisco, Dept Obstet & Gynecol, Human Embryon Stem Cell Program, Inst Regenerat Med, San Francisco, CA 94143 USA
[6] Aduro Biotech, Berkeley, CA USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
DENDRITIC CELLS; IN-VITRO; CYTOMEGALOVIRUS-INFECTION; FLUORESCENT PROTEIN; INTERFERON-GAMMA; EPITHELIAL-CELLS; HUMAN PLACENTA; LIFE-STYLE; E-CADHERIN; CYTOTROPHOBLASTS;
D O I
10.1371/journal.ppat.1002005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Listeria monocytogenes is a facultative intracellular bacterial pathogen that can infect the placenta, a chimeric organ made of maternal and fetal cells. Extravillous trophoblasts (EVT) are specialized fetal cells that invade the uterine implantation site, where they come into direct contact with maternal cells. We have shown previously that EVT are the preferred site of initial placental infection. In this report, we infected primary human EVT with L. monocytogenes. EVT eliminated, similar to 80% of intracellular bacteria over 24-hours. Bacteria were unable to escape into the cytoplasm and remained confined to vacuolar compartments that became acidified and co-localized with LAMP1, consistent with bacterial degradation in lysosomes. In human placental organ cultures bacterial vacuolar escape rates differed between specific trophoblast subpopulations. The most invasive EVT-those that would be in direct contact with maternal cells in vivo-had lower escape rates than trophoblasts that were surrounded by fetal cells and tissues. Our results suggest that EVT present a bottleneck in the spread of L. monocytogenes from mother to fetus by inhibiting vacuolar escape, and thus intracellular bacterial growth. However, if L. monocytogenes is able to spread beyond EVT it can find a more hospitable environment. Our results elucidate a novel aspect of the maternal-fetal barrier.
引用
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页数:11
相关论文
共 70 条
[1]   Listeriosis in the pregnant guinea pig: a model of vertical transmission [J].
Bakardjiev, AI ;
Stacy, BA ;
Fisher, SJ ;
Portnoy, DA .
INFECTION AND IMMUNITY, 2004, 72 (01) :489-497
[2]   Listeria monocytogenes traffics from maternal organs to the placenta and back [J].
Bakardjiev, Anna I. ;
Theriot, Julie A. ;
Portnoy, Daniel A. .
PLOS PATHOGENS, 2006, 2 (06) :623-631
[3]   Placental expression of interferon-γ (IFN-γ) and its receptor IFN-γR2 fail to switch from early hypoxic to late normotensive development in preeclampsia [J].
Banerjee, S ;
Smallwood, A ;
Moorhead, J ;
Chambers, AE ;
Papageorghiou, A ;
Campbell, S ;
Nicolaides, K .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (02) :944-952
[4]  
Bhardwaj V, 1998, J IMMUNOL, V160, P376
[5]   Internalins: a complex family of leucine-rich repeat-containing proteins in Listeria monocytogenes [J].
Bierne, H. ;
Sabet, C. ;
Personnic, N. ;
Cossart, R. .
MICROBES AND INFECTION, 2007, 9 (10) :1156-1166
[6]   Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles [J].
Birmingham, Cheryl L. ;
Canadien, Veronica ;
Kaniuk, Natalia A. ;
Steinberg, Benjamin E. ;
Higgins, Darren E. ;
Brumell, John H. .
NATURE, 2008, 451 (7176) :350-U13
[7]   Localization of type 1 17β-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi [J].
Bonenfant, M ;
Provost, PR ;
Drolet, R ;
Tremblay, Y .
JOURNAL OF ENDOCRINOLOGY, 2000, 165 (02) :217-222
[8]   Perturbation of vacuolar maturation promotes listeriolysin O-independent vacuolar escape during Listeria monocytogenes infection of human cells [J].
Burrack, Laura S. ;
Harper, J. Wade ;
Higgins, Darren E. .
CELLULAR MICROBIOLOGY, 2009, 11 (09) :1382-1398
[9]   A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity [J].
Decatur, AL ;
Portnoy, DA .
SCIENCE, 2000, 290 (5493) :992-995
[10]   Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis [J].
Disson, Olivier ;
Grayo, Solene ;
Huillet, Eugenie ;
Nikitas, Georgios ;
Langa-Vives, Francina ;
Dussurget, Olivier ;
Ragon, Marie ;
Le Monnier, Alban ;
Babinet, Charles ;
Cossart, Pascale ;
Lecuit, Marc .
NATURE, 2008, 455 (7216) :1114-1118