| DOI | Resolve DOI: https://doi.org/10.1016/j.placenta.2013.06.003 |
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| Author | Search for: Nguyen, T.1; Search for: Robinson, N.; Search for: Allison, S.E.; Search for: Coombes, B.K.; Search for: Sad, S.1; Search for: Krishnan, L.1 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | agar; bacterial protein; beta galactosidase; cytokine; interleukin 10; interleukin 10 antibody; interleukin 6; lysosome associated membrane protein 1; pathogenicity island 1 gene effector protein; Rab protein; Rab5 protein; unclassified drug; animal experiment; bacterial load; bacterial strain; bacterium colony; biogenesis; cell division; cell line; cell lysate; cell maturation; cell proliferation; cellular distribution; colony forming unit; confocal microscopy; cytokine production; cytokine response; enzyme release; female; growth inhibition; HeLa cell; human cell; in vitro study; in vivo study; internalization; lysosome; macrophage; mouse; mutant; pathogenicity island; phagocytosis; phagosome; protein localization; Salmonella typhimurium; trophoblast; Western blotting |
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| Abstract | Introduction Salmonella enterica Typhimurium (ST) is a phagosomal pathogen that can infect placental trophoblast cells leading to abortion and severe maternal illness. It is unclear how the trophoblast cells promote profound bacterial proliferation. Methods The mechanism of internalization, intracellular growth and phagosomal biogenesis in ST-infected human epithelial (HeLa), macrophage (THP-1) and trophoblast-derived cell lines (JEG-3, BeWo and HTR-8) was studied. Specific inhibitors were used to block bacterial internalization. Phagosomal maturation was determined by confocal microscopy, Western-blotting and release of lysosomal β-galactosidase by infected cells. Bacterial colony forming units were determined by plating infected cell lysates on agar plates. Results ST proliferated minimally in macrophages but replicated profoundly within trophoblast cells. The ST-ΔinvA (a mutant of Salmonella pathogenicity island-1 gene effector proteins) was unable to infect epithelial cells, but was internalized by scavenger receptors on trophoblasts and macrophages. However, ST was contrastingly localized in early (Rab5+) or late (LAMP1+) phagosomes within trophoblast cells and macrophages respectively. Furthermore trophoblast cells (unlike macrophages) did not exhibit phagoso-lysosomal fusion. ST-infected macrophages produced IL-6 whereas trophoblast cells produced IL-10. Neutralizing IL-10 in JEG-3 cells accelerated phagolysomal fusion and reduced proliferation of ST. Placental bacterial burden was curtailed in vivo in anti-IL-10 antibody treated and IL-10-deficient mice. Discussion Macrophages phagocytose but curtail intracellular replication of ST in late phagosomes. In contrast, phagocytosis by trophoblast cells results in an inappropriate cytokine response and proliferation of ST in early phagosomes. Conclusion IL-10 production by trophoblast cells that delays phagosomal maturation may facilitate proliferation of pathogens in placental cells. © 2013 Elsevier Ltd. All rights reserved. |
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| Publication date | 2013 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21269735 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | fbc072e1-b52b-4dfb-aaa1-6a048f90f6ce |
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| Record created | 2013-12-13 |
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| Record modified | 2020-04-22 |
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