共 60 条
IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses
被引:21
作者:

Gottschalk, Rachel A.
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机构:
NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
Univ Pittsburgh, Dept Immunol, Sch Med, Pittsburgh, PA USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Dorrington, Michael G.
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NIAID, Signaling Syst Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Dutta, Bhaskar
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h-index: 0
机构:
NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
AstraZeneca, Oncol R&D, Gaithersburg, MD USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Krauss, Kathleen S.
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NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Martins, Andrew J.
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h-index: 0
机构:
NIAID, Syst Genom & Bioinformat Unit, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Uderhardt, Stefan
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NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Chan, Waipan
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NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Tsang, John S.
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机构:
NIAID, Syst Genom & Bioinformat Unit, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Torabi-Parizi, Parizad
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机构:
NIH, Crit Care Med Dept, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Fraser, Iain D. C.
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h-index: 0
机构:
NIAID, Signaling Syst Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

Germain, Ronald N.
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h-index: 0
机构:
NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
机构:
[1] NIAID, Lymphocyte Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] NIAID, Signaling Syst Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIAID, Syst Genom & Bioinformat Unit, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[4] NIH, Crit Care Med Dept, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA
[5] Univ Pittsburgh, Dept Immunol, Sch Med, Pittsburgh, PA USA
[6] AstraZeneca, Oncol R&D, Gaithersburg, MD USA
来源:
关键词:
TOLL-LIKE RECEPTOR;
I INTERFERON;
TRANSCRIPTIONAL REPRESSION;
ACTIVATION;
MICE;
RECOGNITION;
EXPRESSION;
INDUCTION;
ENDOCYTOSIS;
REGULATORS;
D O I:
10.7554/eLife.46836
中图分类号:
Q [生物科学];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Despite existing evidence for tuning of innate immunity to different classes of bacteria, the molecular mechanisms used by macrophages to tailor inflammatory responses to specific pathogens remain incompletely defined. By stimulating mouse macrophages with a titration matrix of TLR ligand pairs, we identified distinct stimulus requirements for activating and inhibitory events that evoked diverse cytokine production dynamics. These regulatory events were linked to patterns of inflammatory responses that distinguished between Gram-positive and Gram-negative bacteria, both in vitro and after in vivo lung infection. Stimulation beyond a TLR4 threshold and Gram-negative bacteria-induced responses were characterized by a rapid type I IFN-dependent decline in inflammatory cytokine production, independent of IL-10, whereas inflammatory responses to Gram-positive species were more sustained due to the absence of this IFN-dependent regulation. Thus, disparate triggering of a cytokine negative feedback loop promotes tuning of macrophage responses in a bacteria class-specific manner and provides context-dependent regulation of inflammation dynamics.
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页数:23
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