Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.
Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.
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.
e1002814
Daigneault, Marc
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De Silva, Thushan I
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Bewley, Martin A.
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Preston, Julie A.
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Marriott, Helen M.
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Mitchell, Andrea M.
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Mitchell, Timothy J.
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Read, Robert C.
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Whyte, Moira K. B.
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Dockrell, David H.
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19 July 2012
Daigneault, Marc
4d84aabf-c0cd-463d-b7be-80d13f66b180
De Silva, Thushan I
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Bewley, Martin A.
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Preston, Julie A.
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Marriott, Helen M.
34ca8904-d637-4081-b34c-12be45ecef9f
Mitchell, Andrea M.
dbffe013-45ea-42f2-ba26-d4ff36593927
Mitchell, Timothy J.
56ddfd4d-d6f7-4250-8864-17f156904f95
Read, Robert C.
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Whyte, Moira K. B.
fed8c25b-ced7-4a16-89f3-b93208a63a18
Dockrell, David H.
a068c9bf-35b8-4c10-8f91-58639cfeca0b
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. and Dockrell, David H.
(2012)
Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.
PLOS Pathogens, 8 (7), .
(doi:10.1371/journal.ppat.1002814).
(PMID:22829769)
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.
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Published date: 19 July 2012
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 346733
URI: http://eprints.soton.ac.uk/id/eprint/346733
ISSN: 1553-7366
PURE UUID: 977aad57-ed8f-4806-872f-fd9d069af263
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Date deposited: 23 Jan 2013 11:26
Last modified: 15 Mar 2024 03:42
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Author:
Marc Daigneault
Author:
Thushan I De Silva
Author:
Martin A. Bewley
Author:
Julie A. Preston
Author:
Helen M. Marriott
Author:
Andrea M. Mitchell
Author:
Timothy J. Mitchell
Author:
Moira K. B. Whyte
Author:
David H. Dockrell
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