CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex.
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.
Wu
Weihui
W
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hsu
Yen-Michael S
YM
Bi
Liangkuan
L
Songyang
Zhou
Z
Lin
Xin
X
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002176:Candida albicans / Q000276:immunology; D002460:Cell Line; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008089:Listeria monocytogenes / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000276:immunology* / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D020730:Guanine Nucleotide Dissociation Inhibitors; D009479:Neuropeptides; D011506:Proteins; C484602:Rac1 protein, mouse; D017382:Reactive Oxygen Species; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein