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Gamma interferon enhances internalization and early nonoxidative killing of Salmonella enterica serovar Typhimurium by human macrophages and modifies cytokine responses

Gamma interferon enhances internalization and early nonoxidative killing of Salmonella enterica serovar Typhimurium by human macrophages and modifies cytokine responses
Gamma interferon enhances internalization and early nonoxidative killing of Salmonella enterica serovar Typhimurium by human macrophages and modifies cytokine responses

Gamma interferon (IFN-gamma) is a critical cytokine in host defense against salmonella infections, but its role in phagocytic killing of intracellular Salmonella spp. has been investigated mainly in animal rather than human cells. We measured the effect of recombinant IFN-gamma (rIFN-gamma) priming on bacterial internalization, intracellular killing, oxidative burst, and cytokine release during phagocytosis of Salmonella enterica serovar Typhimurium by human monocyte-derived macrophages (MDM). Eleven-day-old MDM, primed for 72 h with rIFN-gamma (100 ng/ml) exhibited an increased proportion of cells with associated bacteria (31% versus 26%, P = 0.036) and a 67% increase in internalized bacteria per cell compared to unprimed cells (P = 0.025). Retrieval of viable bacteria following internalization was reduced 3.6-fold in 72-h primed versus unprimed MDM (interquartile range, 3.1 to 6.4) at 0.5 h due to enhanced early intracellular killing, and this difference was maintained up to 24 h. In contrast, cells primed for only 24 h exhibited no increase in early killing. MDM were competent to produce an early oxidative burst when stimulated with phorbol myristate acetate, which was fully abrogated by the respiratory burst inhibitor diphenyleneiodonium chloride (DPI), but infection of MDM with S. enterica serovar Typhimurium did not cause an increase in the early respiratory burst under unprimed or primed conditions, and DPI had no effect on the early killing of bacteria by primed or unprimed MDM. During 24 h following infection, rIFN-gamma-primed MDM released more interleukin-12 (IL-12) and less IL-10 relative to unprimed cells. We conclude that 72-h priming with rIFN-gamma increases the efficiency of internalization and nonoxidative early intracellular killing of S. enterica serovar Typhimurium by human macrophages and modifies subsequent cytokine release.

Adult, Cytokines, Humans, Interferon-gamma, Interleukin-10, Interleukin-12, Macrophages, Middle Aged, Recombinant Proteins, Salmonella typhimurium, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
0019-9567
3445-3452
Gordon, Melita A.
d63b6bc8-5b49-4848-9910-35885e6bc563
Jack, Dominic L.
246dc47b-5b5e-4933-9227-d13aafd9cb88
Dockrell, David H.
a068c9bf-35b8-4c10-8f91-58639cfeca0b
Lee, Margaret E.
a87d108c-c8e3-420c-be05-e7e23ee0619e
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Gordon, Melita A.
d63b6bc8-5b49-4848-9910-35885e6bc563
Jack, Dominic L.
246dc47b-5b5e-4933-9227-d13aafd9cb88
Dockrell, David H.
a068c9bf-35b8-4c10-8f91-58639cfeca0b
Lee, Margaret E.
a87d108c-c8e3-420c-be05-e7e23ee0619e
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Gordon, Melita A., Jack, Dominic L., Dockrell, David H., Lee, Margaret E. and Read, Robert C. (2005) Gamma interferon enhances internalization and early nonoxidative killing of Salmonella enterica serovar Typhimurium by human macrophages and modifies cytokine responses. Infection and Immunity, 73 (6), 3445-3452. (doi:10.1128/IAI.73.6.3445-3452.2005).

Record type: Article

Abstract

Gamma interferon (IFN-gamma) is a critical cytokine in host defense against salmonella infections, but its role in phagocytic killing of intracellular Salmonella spp. has been investigated mainly in animal rather than human cells. We measured the effect of recombinant IFN-gamma (rIFN-gamma) priming on bacterial internalization, intracellular killing, oxidative burst, and cytokine release during phagocytosis of Salmonella enterica serovar Typhimurium by human monocyte-derived macrophages (MDM). Eleven-day-old MDM, primed for 72 h with rIFN-gamma (100 ng/ml) exhibited an increased proportion of cells with associated bacteria (31% versus 26%, P = 0.036) and a 67% increase in internalized bacteria per cell compared to unprimed cells (P = 0.025). Retrieval of viable bacteria following internalization was reduced 3.6-fold in 72-h primed versus unprimed MDM (interquartile range, 3.1 to 6.4) at 0.5 h due to enhanced early intracellular killing, and this difference was maintained up to 24 h. In contrast, cells primed for only 24 h exhibited no increase in early killing. MDM were competent to produce an early oxidative burst when stimulated with phorbol myristate acetate, which was fully abrogated by the respiratory burst inhibitor diphenyleneiodonium chloride (DPI), but infection of MDM with S. enterica serovar Typhimurium did not cause an increase in the early respiratory burst under unprimed or primed conditions, and DPI had no effect on the early killing of bacteria by primed or unprimed MDM. During 24 h following infection, rIFN-gamma-primed MDM released more interleukin-12 (IL-12) and less IL-10 relative to unprimed cells. We conclude that 72-h priming with rIFN-gamma increases the efficiency of internalization and nonoxidative early intracellular killing of S. enterica serovar Typhimurium by human macrophages and modifies subsequent cytokine release.

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More information

Published date: June 2005
Keywords: Adult, Cytokines, Humans, Interferon-gamma, Interleukin-10, Interleukin-12, Macrophages, Middle Aged, Recombinant Proteins, Salmonella typhimurium, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.

Identifiers

Local EPrints ID: 416379
URI: http://eprints.soton.ac.uk/id/eprint/416379
ISSN: 0019-9567
PURE UUID: 12ec13c4-ee61-449c-b921-f257dc7277c0
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 14 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30

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Contributors

Author: Melita A. Gordon
Author: Dominic L. Jack
Author: David H. Dockrell
Author: Margaret E. Lee
Author: Robert C. Read ORCID iD

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