• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals.

Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1β/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed pronounced caspase-1 and IL-1β/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery.

Pubmed ID: 22461501

Authors

  • Shenoy AR
  • Wellington DA
  • Kumar P
  • Kassa H
  • Booth CJ
  • Cresswell P
  • MacMicking JD

Journal

Science (New York, N.Y.)

Publication Data

April 27, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI068041-06
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alum Compounds
  • Animals
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Caspase 1
  • Cell Line
  • Cytoskeletal Proteins
  • GTP-Binding Proteins
  • Humans
  • Inflammasomes
  • Interferon-gamma
  • Interleukin-1beta
  • Lipopolysaccharides
  • Listeria monocytogenes
  • Listeriosis
  • Macrophages
  • Mice
  • Protein Multimerization
  • RNA Interference
  • Salmonella typhimurium
  • Uric Acid