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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
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
0022-1899
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
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), 713-722. (doi:10.1086/323084).

Record type: Article

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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More information

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

Identifiers

Local EPrints ID: 416808
URI: https://eprints.soton.ac.uk/id/eprint/416808
ISSN: 0022-1899
PURE UUID: 3fe55c75-bf00-4567-90f0-83e1a0a1c78c
ORCID for R.C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 10 Jan 2018 17:30
Last modified: 14 Mar 2019 01:36

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