IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses

Gottschalk RA, Dorrington MG, Dutta B, Krauss KS, Martins AJ, Uderhardt S, Chan W, Tsang JS, Torabi-Parizi P, Fraser IDC, Germain RN (2019)

Publication Type: Journal article

Publication year: 2019

Journal

eLife eLife Sciences Publications

Book Volume: 8

Article Number: e46836

DOI: 10.7554/eLife.46836

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.

Authors with CRIS profile

Stefan Uderhardt

Involved external institutions

US National Institutes of Health (NIH) US United States (USA) (US)

How to cite

APA:

Gottschalk, R.A., Dorrington, M.G., Dutta, B., Krauss, K.S., Martins, A.J., Uderhardt, S.,... Germain, R.N. (2019). IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses. eLife, 8. https://doi.org/10.7554/eLife.46836

MLA:

Gottschalk, Rachel A., et al. "IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses." eLife 8 (2019).

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