IL-10 produced by trophoblast cells inhibits phagosome maturation leading to profound intracellular proliferation of Salmonella enterica Typhimurium

Download
  1. Get@NRC: IL-10 produced by trophoblast cells inhibits phagosome maturation leading to profound intracellular proliferation of Salmonella enterica Typhimurium (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1016/j.placenta.2013.06.003
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titlePlacenta
ISSN0143-4004
Volume34
Issue9
Pages765774; # of pages: 10
Subjectagar; 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; article; bacterial load; bacterial strain; bacterium colony; biogenesis; cell division; cell line; cell lysate; cell maturation; cell proliferation; cellular distribution; colony forming unit; confocal microscopy; controlled study; cytokine production; cytokine response; enzyme release; female; growth inhibition; HeLa cell; human; human cell; in vitro study; in vivo study; internalization; lysosome; macrophage; mouse; mutant; nonhuman; pathogenicity island; phagocytosis; phagosome; priority journal; protein localization; Salmonella typhimurium; trophoblast; Western blotting
AbstractIntroduction 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.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics (HHT-TSH)
Peer reviewedYes
NPARC number21269735
Export citationExport as RIS
Report a correctionReport a correction
Record identifierfbc072e1-b52b-4dfb-aaa1-6a048f90f6ce
Record created2013-12-13
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)