An essential role for RIG-I in toll-like receptor-stimulated phagocytosis.
Retinoic acid-inducible gene-I (RIG-I) plays an important role in antiviral response by recognizing double-stranded RNA. Here we demonstrate an unanticipated role of RIG-I in Toll-like receptor (TLR)-stimulated phagocytosis. Stimulation with lipopolysaccharide (LPS), a ligand of TLR4, induced the expression of RIG-I in macrophages. Depletion of RIG-I by RNAi or gene targeting inhibited the LPS-induced phagocytosis of bacteria. Cellular processes involved in phagocytosis, such as small GTPase Cdc42/Rac1 activation, actin polymerization, and actin-regulator Arp2/3 recruitment, were also impaired in RIG-I-deficient macrophages activated by LPS. Moreover, RIG-I(-/-) mice were found to be more susceptible to infection with Escherichia coli as compared to wild-type mice. Thus, the regulatory functions of RIG-I are strikingly broad, including a role not only in antiviral responses but in antibacterial responses as well.
Kong
Ling
L
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
Sun
Lei
L
Zhang
Hongxin
H
Liu
Qin
Q
Liu
Ye
Y
Qin
Linhua
L
Shi
Guojun
G
Hu
Jun-Hao
JH
Xu
Ajing
A
Sun
Yue-Ping
YP
Li
Dangsheng
D
Shi
Yu-Fang
YF
Zang
Jing-Wu
JW
Zhu
Jiang
J
Chen
Zhu
Z
Wang
Zhu-Gang
ZG
Ge
Bao-Xue
BX
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020868:Gene Silencing; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
D051376:Actin-Related Protein 2-3 Complex; C115491:Arhgap31 protein, mouse; D020690:GTPase-Activating Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; D051197:Toll-Like Receptor 4; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein