Journal Article

PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells

Takuma Shibata, Naoki Takemura, Yuji Motoi, Yoshiyuki Goto, Thangaraj Karuppuchamy, Kumi Izawa, Xiaobing Li, Sachiko Akashi-Takamura, Natsuko Tanimura, Jun Kunisawa, Hiroshi Kiyono, Shizuo Akira, Toshio Kitamura, Jiro Kitaura, Satoshi Uematsu and Kensuke Miyake

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 10, pages 613-623
Published in print October 2012 |
Published online July 2012 | | DOI: http://dx.doi.org/10.1093/intimm/dxs068

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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.

Keywords: flagellin; innate immunity; TLR5

Journal Article.  6640 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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