A Rapid Caspase-11 Response Induced by IFN γ Priming Is Independent of Guanylate Binding Proteins

Sky W Brubaker; Susan M Brewer; Liliana M Massis; Brooke A Napier; Denise M Monack

doi:10.1016/j.isci.2020.101612

A Rapid Caspase-11 Response Induced by IFN γ Priming Is Independent of Guanylate Binding Proteins

iScience. 2020 Sep 29;23(10):101612. doi: 10.1016/j.isci.2020.101612. eCollection 2020 Oct 23.

Authors

Sky W Brubaker¹, Susan M Brewer¹, Liliana M Massis¹, Brooke A Napier², Denise M Monack¹

Affiliations

¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Biology Department, Portland State University, Portland, OR 97201, USA.

Abstract

In mammalian cells, inflammatory caspases detect Gram-negative bacterial invasion by binding lipopolysaccharides (LPS). Murine caspase-11 binds cytosolic LPS, stimulates pyroptotic cell death, and drives sepsis pathogenesis. Extracellular priming factors enhance caspase-11-dependent pyroptosis. Herein we compare priming agents and demonstrate that IFNγ priming elicits the most rapid and amplified macrophage response to cytosolic LPS. Previous studies indicate that IFN-induced expression of caspase-11 and guanylate binding proteins (GBPs) are causal events explaining the effects of priming on cytosolic LPS sensing. We demonstrate that these events cannot fully account for the increased response triggered by IFNγ treatment. Indeed, IFNγ priming elicits higher pyroptosis levels in response to cytosolic LPS when macrophages stably express caspase-11. In macrophages lacking GBPs encoded on chromosome 3, IFNγ priming enhanced pyroptosis in response to cytosolic LPS as compared with other priming agents. These results suggest an unknown regulator of caspase-11-dependent pyroptosis exists, whose activity is upregulated by IFNγ.

Keywords: Cell Biology; Immunology.

Abstract

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