New cytosolic pattern recognition receptor for bacterial LPS
In a new article in Nature Communications Jose Santos and Dave Boucher from Prof. Petr Broz’s lab identify guanylate-binding protein 1 (GBP1) as a new cytosolic receptor for Gram-negative bacterial Lipopolysaccharide (LPS) in human cells. Investigating the cytosolic immune response to the bacterium Salmonella typhimurium, they find that GBP1 covers the bacterial surface seconds after bacterial entry into the cytosol by interacting with the negatively charged LPS core region. GBP1 then recruits additional GBP family members, notably GBP2-4, to assemble a ‘GBP coat’ around the whole bacterium. This complex then promotes the recruitment and activation of human caspase-4, a protease that drives host cell death and IL-18 production to restrict bacterial growth and alert the immune system. This study provides the first evidence that guanylate-binding proteins, a group of interferon-induced GTPases found in both humans and mice, act as pattern recognition receptors.