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J. Exp. Med.,
Volume 189, Number 11, June 7, 1999 1777-1782
By
From the Department of Immunology, Saga Medical School, Saga, Japan
Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently
been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However,
transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a
requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface
and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling.
Identification of this new receptor complex has potential implications for understanding host
defense, as well as pathophysiologic, mechanisms.
B;
signaling
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