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IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses
- Source :
- eLife, Vol 8 (2019), eLife
- Publication Year :
- 2019
- Publisher :
- eLife Sciences Publications, Ltd, 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Mouse
QH301-705.5
Science
medicine.medical_treatment
Inflammation
Stimulation
macrophage
Gram-Positive Bacteria
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Immunology and Inflammation
0302 clinical medicine
In vivo
Gram-Negative Bacteria
Pneumonia, Bacterial
medicine
Animals
Biology (General)
Cells, Cultured
Feedback, Physiological
Innate immune system
General Immunology and Microbiology
biology
Macrophages
General Neuroscience
negative feedback
General Medicine
biology.organism_classification
In vitro
Cell biology
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Cytokine
inflammation
Interferon Type I
TLR4
Cytokines
Medicine
medicine.symptom
signal integration
type I IFN
Bacteria
Research Article
Computational and Systems Biology
030215 immunology
Subjects
Details
- ISSN :
- 2050084X
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....7f6bd5523e0673a759382984c5d0754f
- Full Text :
- https://doi.org/10.7554/elife.46836