title: TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection.
abstract: Phagocytosis and oxidative burst are two major effector arms of innate immunity. Although it is known that both are activated by Toll-like receptors (TLRs) and Rac GTPases, how their strengths are controlled in quiescent and TLR-activated cells is not clear. We report here that TIPE2 (TNFAIP8L2) serves as a negative regulator of innate immunity by linking TLRs to Rac. TLRs control the expression levels of TIPE2, which in turn dictates the strengths of phagocytosis and oxidative burst by binding to and blocking Rac GTPases. Consequently, TIPE2 knockout cells have enhanced phagocytic and bactericidal activities and TIPE2 knockout mice are resistant to bacterial infection. Thus, TIPE2 sets the strengths of phagocytosis and oxidative burst and may be targeted to effectively control infections.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Wang
authors.forename: Svetlana
authors.initials: S
authors.lastname: Fayngerts
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Honghong
authors.initials: H
authors.lastname: Sun
authors.forename: Derek S
authors.initials: DS
authors.lastname: Johnson
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ruan
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003433:Crosses, Genetic; D006801:Humans; D006868:Hydrolysis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D021381:Protein Transport; D016897:Respiratory Burst / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C529002:TIPE2 protein, mouse; C552057:TNFAIP8L2 protein, human; D051193:Toll-Like Receptors; D020744:rac GTP-Binding Proteins