Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis
Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis
Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.
Amino Acid Chloromethyl Ketones, Apoptosis, Caspase Inhibitors, Cells, Cultured, Cysteine Proteinase Inhibitors, Humans, In Situ Nick-End Labeling, Macrophages, Monocytes, Phagocytosis, Reference Values, Regression Analysis, Streptococcus pneumoniae, Time Factors, Journal Article, Research Support, Non-U.S. Gov't
713-722
Dockrell, D.H.
df2521bf-534f-4798-9b1d-1c02f7e72713
Lee, M.
d0e603c6-91c1-44f3-952e-88d38aa4191c
Lynch, D.H.
de3d7fdd-f43d-45af-8bb1-4a1ce2843f96
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
15 September 2001
Dockrell, D.H.
df2521bf-534f-4798-9b1d-1c02f7e72713
Lee, M.
d0e603c6-91c1-44f3-952e-88d38aa4191c
Lynch, D.H.
de3d7fdd-f43d-45af-8bb1-4a1ce2843f96
Read, R.C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Dockrell, D.H., Lee, M., Lynch, D.H. and Read, R.C.
(2001)
Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are associated with direct and bystander macrophage apoptosis.
The Journal of Infectious Diseases, 184 (6), .
(doi:10.1086/323084).
Abstract
Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.
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Published date: 15 September 2001
Keywords:
Amino Acid Chloromethyl Ketones, Apoptosis, Caspase Inhibitors, Cells, Cultured, Cysteine Proteinase Inhibitors, Humans, In Situ Nick-End Labeling, Macrophages, Monocytes, Phagocytosis, Reference Values, Regression Analysis, Streptococcus pneumoniae, Time Factors, Journal Article, Research Support, Non-U.S. Gov't
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Local EPrints ID: 416808
URI: http://eprints.soton.ac.uk/id/eprint/416808
ISSN: 0022-1899
PURE UUID: 3fe55c75-bf00-4567-90f0-83e1a0a1c78c
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Date deposited: 10 Jan 2018 17:30
Last modified: 16 Mar 2024 04:10
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Author:
D.H. Dockrell
Author:
M. Lee
Author:
D.H. Lynch
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