An Essential Role for RIG-I in Toll-like Receptor-Stimulated Phagocytosis

Ling Kong1,4,6,Lei Sun1,4,6,Hongxin Zhang2,Qin Liu1,Ye Liu1,Linhua Qin1,Guojun Shi1,4,Jun-Hao Hu1,4,Ajing Xu1,Yue-Ping Sun2,Dangsheng Li5,Yu-Fang Shi1,Jing-Wu Zang1,Jiang Zhu3,Zhu Chen3,Zhu-Gang Wang2,3,,andBao-Xue Ge1,,

1 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
2 Laboratory of Genetic Engineering, Department of Medical Genetics, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
3 State Key Laboratory for Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai 200025, China
4 Graduate School of Chinese Academy of Sciences, Beijing 100039, China
5 Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

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.