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Lipopeptides are signaled by Toll-like receptor 1, 2 and 6 in endolysosomes.

International immunology (2014-05-27)
Yuji Motoi, Takuma Shibata, Koichiro Takahashi, Atsuo Kanno, Yusuke Murakami, Xiaobing Li, Tadashi Kasahara, Kensuke Miyake
ABSTRACT

Toll-like receptors (TLRs) recognize a variety of microbial products and induce defense responses. Pathogen sensing by TLRs occurs either on the cell surface or in endolysosomes. TLR-dependent responses are greatly influenced by the site of pathogen sensing. TLR heterodimers TLR1/TLR2 and TLR2/TLR6 recognize tri- or diacylated microbial lipopeptides, respectively. Although TLR1, 2 and 6 are believed to localize on the cell surface of immune cells, little is known about where lipopeptides are signaled. In this study, we established mAbs to TLR1, 2 and 6. TLR1, 2 and 6 were expressed on the surface of B cells, monocytes and dendritic cells in a manner dependent on a TLR-specific chaperone PRAT4A (protein associated with TLR4 A). Cell surface localization of TLR1 or TLR6 was not necessarily required for TLR2 response. Furthermore, a dynamin inhibitor 'Dynasore' abolished the lipopeptide responses by preventing lipopeptide internalization into LAMP-1 and LAMP-2 positive compartments. Our findings suggest that lipopeptides elicit TLR1/2 and TLR2/6 signaling in the endolysosomes, but not on the cell surface.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
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