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Journal of Endotoxin Research, Vol. 10, No. 6, 406-412 (2004)
DOI: 10.1177/09680519040100060501

Mechanisms of TLR9 activation

Eicke Latz

Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA, eicke.latz{at}umassmed.edu

Alberto Visintin

Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Terje Espevik

Norwegian University of Science and Technology, Trondheim, Norway

Douglas T. Golenbock

Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Non-methylated CpG-motifs in bacterial or viral DNA are recognized by TLR9 as foreign. The activation of TLR9 by microbial DNA or synthetic oligonucleotides based on these motifs leads to the induction of innate immune responses. We have compared the subcellular localization of fluorescent versions of TLR9 and TLR4 and found that TLR9 is expressed in the endoplasmic reticulum while TLR4 is expressed on the plasma membrane. Fluorescently tagged bacterial DNA or CpG-DNA was observed to traffic to a tubular lysosomal compartment in human pDCs. In stimulated cells, TLR9 translocated to CpG-DNA or microbial DNA containing structures in the endosome, where TLR9 binds to DNA and initiates signaling.

Key Words: Toll-like receptors • innate immunity • phagocytosis • CpG-DNA


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