We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.
- Authors
Daigneault, Marc; De Silva, Thushan I; Bewley, Martin A; Preston, Julie A; Marriott, Helen M; Mitchell, Andrea M; Mitchell, Timothy J; Read, Robert C; Whyte, Moira K B; Dockrell, David H
- 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.
- Publication
PLoS pathogens, 2012, Vol 8, Issue 7, pe1002814
- ISSN
1553-7374
- Publication type
Journal Article
- DOI
10.1371/journal.ppat.1002814