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Guanylate Binding Protein 1 (GBP1): A Key Protein in Inflammatory Pyroptosis

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Abstract

Scientists recently made a significant breakthrough in the recognition of pathogens via guanylate binding protein 1 (GBP1). Wandel et al. [1] in Nature Immunology described their findings where GBP1 acts as a pattern recognition receptor that directly connects to lipopolysaccharide (LPS). GBP1 identifies gram-negative bacteria such as the enteric pathogen, Salmonella enterica serovar Typhimurium, that enter the cytoplasm of the host cell. GBP1 then quickly connects to LPS and stimulates the assembly of more GBPs in the order of GBP2, GBP3, and GBP4. Subsequently, inflammatory caspase-4 arrives at the GBP1–4 activation platform. Next, the activated caspase-4 drives the cleavage of Gasdermin D, triggering the release of the pro-inflammatory cytokine, interleukin-18 (IL-18) leading to inflammatory pyroptosis and cell death. Not only do these remarkable results expand our current understanding of GBP1, but they also carry the potential to develop therapeutic targets for inflammasome-mediated human disorders.

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Acknowledgements

We thank Brenda Flam, Ph.D. (University of South Florida) and Mason Breitzig, MPH (Pennsylvania State University College of Medicine) for comments and revisions on our manuscript.

Funding

The L. Galam laboratory was funded by USF Foundation funds, Joy McCann Culverhouse Chair in Allergy & Immunology and Mabel & Ellsworth Simmons Professorship for Asthma Research.

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  1. Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Colleen Elsa Johns & Lakshmi Galam

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  1. Colleen Elsa Johns
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  2. Lakshmi Galam
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Correspondence to Lakshmi Galam.

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Johns, C.E., Galam, L. Guanylate Binding Protein 1 (GBP1): A Key Protein in Inflammatory Pyroptosis. Cell Biochem Biophys 80, 295–299 (2022). https://doi.org/10.1007/s12013-021-01056-y

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