title: PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells.
abstract: AbstractToll-like receptor 5 (TLR5), a sensor for bacterial flagellin, mounts innate and adaptive immune responses, and has been implicated in infectious diseases, colitis and metabolic syndromes. Although TLR5 is believed to belong to cell surface TLRs, cell surface expression has never been verified. Moreover, it has remained unclear which types of immune cells express TLR5 and contribute to flagellin-dependent responses. In this study we established an anti-mouse TLR5 monoclonal antibody and studied the cell surface expression of TLR5 on immune cells. The macrophage cell line J774 expressed endogenous TLR5 on the cell surface and produced IL-6 and G-CSF in response to flagellin. Cell surface expression of TLR5 and flagellin-induced responses were completely abolished by silencing a TLR-specific chaperone protein associated with TLR4 A (PRAT4A), demonstrating that TLR5 is another client of PRAT4A. In the in vivo immune cells, cell surface TLR5 was mainly found on neutrophils and CD11b (hi) Ly6C (hi) classical monocytes in the bone marrow, circulation, spleen and inflammatory lesions. Ly6C (hi) classical monocytes, but not neutrophils, produced cytokines in response to flagellin. Splenic CD8 (-) CD4 (+) conventional dendritic cells and CD11c (hi) CD11b (hi) lamina propria DCs, also clearly expressed cell surface TLR5. Collectively, cell surface expression of TLR5 is dependent on PRAT4A and restricted to neutrophils, classical monocytes and specific DC subsets.
authors: Division of Infectious Genetics, Department of Microbiology and Immunology, University of Tokyo, Minatoku, Tokyo108-8639, Japan.
authors: Takuma
authors: T
authors: Shibata
authors: Naoki
authors: N
authors: Takemura
authors: Yuji
authors: Y
authors: Motoi
authors: Yoshiyuki
authors: Y
authors: Goto
authors: Thangaraj
authors: T
authors: Karuppuchamy
authors: Kumi
authors: K
authors: Izawa
authors: Xiaobing
authors: X
authors: Li
authors: Sachiko
authors: S
authors: Akashi-Takamura
authors: Natsuko
authors: N
authors: Tanimura
authors: Jun
authors: J
authors: Kunisawa
authors: Hiroshi
authors: H
authors: Kiyono
authors: Shizuo
authors: S
authors: Akira
authors: Toshio
authors: T
authors: Kitamura
authors: Jiro
authors: J
authors: Kitaura
authors: Satoshi
authors: S
authors: Uematsu
authors: Kensuke
authors: K
authors: Miyake
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005408:Flagellin / Q000378:metabolism; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C508076:TLR4-associated protein, mouse; D051198:Toll-Like Receptor 5; D005408:Flagellin