Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q

Mariko Yoshizaki, Aya Tazawa, Eiji Kasumi, Shigemi Sasawatari, Kenji Itoh, Taeko Dohi, Takehiko Sasazuki, Kayo Inaba, Andrew P. Makrigiannis, Noriko Toyama-Sorimachi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Toll-like receptor (TLR) 9 recognizes unmethylated microorganismal cytosine guanine dinucleotide (CpG) DNA and elicits innate immune responses. However, the regulatory mechanisms of the TLR signaling remain elusive. We recently reported that Ly49Q, an immunoreceptor tyrosine-based inhibitory motif-bearing inhibitory receptor belonging to the natural killer receptor family, is crucial for TLR9-mediated type I interferon production by plasmacytoid dendritic cells. Ly49Q is expressed in plasmacytoid dendritic cells, macrophages, and neutrophils, but not natural killer cells. In this study, we showed that Ly49Q regulates TLR9 signaling by affecting endosome/lysosome behavior. Ly49Q colocalized with CpG in endosome/lysosome compartments. Cells lacking Ly49Q showed a disturbed redistribution of TLR9 and CpG. In particular, CpG-induced tubular endolysosomal extension was impaired in the absence of Ly49Q. Consistent with these findings, cells lacking Ly49Q showed impaired cytokine production in response to CpG-oligodeoxynucleotide. Our data highlight a novel mechanism by which TLR9 signaling is controlled through the spatiotemporal regulation of membrane trafficking by the immunoreceptor tyrosine-based inhibitory motif-bearing receptor Ly49Q.

Original languageEnglish
Pages (from-to)1518-1527
Number of pages10
JournalBlood
Volume114
Issue number8
DOIs
Publication statusPublished - Nov 19 2009

Fingerprint

Toll-Like Receptor 9
Endosomes
Bearings (structural)
Lysosomes
Dendritic Cells
Tyrosine
Interferon Type I
Oligodeoxyribonucleotides
Toll-Like Receptors
Innate Immunity
Natural Killer Cells
Neutrophils
Macrophages
Cytokines
Membranes
DNA
cytidylyl-3'-5'-guanosine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Yoshizaki, M., Tazawa, A., Kasumi, E., Sasawatari, S., Itoh, K., Dohi, T., ... Toyama-Sorimachi, N. (2009). Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. Blood, 114(8), 1518-1527. https://doi.org/10.1182/blood-2008-12-192344

Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. / Yoshizaki, Mariko; Tazawa, Aya; Kasumi, Eiji; Sasawatari, Shigemi; Itoh, Kenji; Dohi, Taeko; Sasazuki, Takehiko; Inaba, Kayo; Makrigiannis, Andrew P.; Toyama-Sorimachi, Noriko.

In: Blood, Vol. 114, No. 8, 19.11.2009, p. 1518-1527.

Research output: Contribution to journalArticle

Yoshizaki, M, Tazawa, A, Kasumi, E, Sasawatari, S, Itoh, K, Dohi, T, Sasazuki, T, Inaba, K, Makrigiannis, AP & Toyama-Sorimachi, N 2009, 'Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q', Blood, vol. 114, no. 8, pp. 1518-1527. https://doi.org/10.1182/blood-2008-12-192344
Yoshizaki, Mariko ; Tazawa, Aya ; Kasumi, Eiji ; Sasawatari, Shigemi ; Itoh, Kenji ; Dohi, Taeko ; Sasazuki, Takehiko ; Inaba, Kayo ; Makrigiannis, Andrew P. ; Toyama-Sorimachi, Noriko. / Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. In: Blood. 2009 ; Vol. 114, No. 8. pp. 1518-1527.
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