CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex.

Abstract	In response to invading microorganisms, macrophages engage in phagocytosis and rapidly release reactive oxygen species (ROS), which serve an important microbicidal function. However, how phagocytosis induces ROS production remains largely unknown. CARD9, a caspase-recruitment domain (CARD)-containing protein, is important for resistance to fungal and bacterial infection. The mechanism of CARD9-mediated bacterial clearance is still mostly unknown. Here we show that CARD9 is required for killing intracellular bacteria in macrophages. CARD9 associated with the GDP-dissociation inhibitor LyGDI in phagosomes after bacterial and fungal infection and binding of CARD9 suppressed LyGDI-mediated inhibition of the GTPase Rac1, thereby leading to ROS production and bacterial killing in macrophages. Thus, our studies identify a key pathway that leads to microbe-elicited ROS production.
Authors	Weihui Wu, Yen-Michael S Hsu, Liangkuan Bi, Zhou Songyang, Xin Lin
Journal	Nature immunology (Nat Immunol) Vol. 10 Issue 11 Pg. 1208-14 (Nov 2009) ISSN: 1529-2916 [Electronic] United States
PMID	19767757 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing CARD Signaling Adaptor Proteins Card9 protein, mouse Guanine Nucleotide Dissociation Inhibitors Neuropeptides Proteins Rac1 protein, mouse Reactive Oxygen Species rho-Specific Guanine Nucleotide Dissociation Inhibitors rac GTP-Binding Proteins rac1 GTP-Binding Protein
Topics	Adaptor Proteins, Signal Transducing (immunology) Animals CARD Signaling Adaptor Proteins Candida albicans (immunology) Cell Line Guanine Nucleotide Dissociation Inhibitors (immunology, metabolism) Immunity, Innate Listeria monocytogenes (immunology) Macrophages (immunology, microbiology) Mice Mice, Knockout Neuropeptides (immunology, metabolism) Phagosomes (immunology, microbiology) Proteins (immunology, metabolism) Reactive Oxygen Species (immunology, metabolism) rac GTP-Binding Proteins (immunology, metabolism) rac1 GTP-Binding Protein rho-Specific Guanine Nucleotide Dissociation Inhibitors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!