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.
Original language | English |
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Pages (from-to) | e1002814 |
Journal | PLoS pathogens |
Volume | 8 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2012 |
Keywords
- 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