Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection

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 H Dockrell

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)e1002814
JournalPLoS pathogens
Issue number7
Publication statusPublished - 2012


  • Animals
  • Antigens, CD14
  • Antigens, CD3
  • Apoptosis
  • Bacteremia
  • Bacterial Proteins
  • Cells, Cultured
  • Fas Ligand Protein
  • HIV Infections
  • HIV-1
  • Humans
  • Imidazoles
  • Indoles
  • Lung
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes
  • Necrosis
  • Pneumococcal Infections
  • Streptococcus pneumoniae
  • Streptolysins
  • T-Lymphocytes


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