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Monocytes Regulate the Mechanism of T-cell Death by Inducing Fas-Mediated Apoptosis during Bacterial Infection

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  • Marc Daigneault
  • Thushan I. De Silva
  • Martin A. Bewley
  • Julie A. Preston
  • Helen M. Marriott
  • Andrea M. Mitchell
  • Timothy J. Mitchell
  • Robert C. Read
  • Moira K. B. Whyte
  • David Dockrell

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    Rights statement: Copyright: © 2012 Daigneault et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002814
Original languageEnglish
Article number1002814
Number of pages16
JournalPLoS Pathogens
Volume8
Issue number7
DOIs
Publication statusPublished - 19 Jul 2012

Abstract

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3+ T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease.

    Research areas

  • ALVEOLAR MACROPHAGE APOPTOSIS, TUMOR-NECROSIS-FACTOR, STREPTOCOCCUS-PNEUMONIAE, LYMPHOCYTE APOPTOSIS, PNEUMOCOCCAL PNEUMONIA, MICROBIAL PATHOGENS, FLOW-CYTOMETRY, PNEUMOLYSIN, LIGAND, INDUCTION

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