Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Search research articles

Related Experiment Videos

TLR4 as the mammalian endotoxin sensor.

¹Department of Immunology, Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. brūce@scripps.edu

Current Topics in Microbiology and Immunology

|December 7, 2002

Summary

The discovery of Toll-like receptor 4 (TLR4) as the central component of the lipopolysaccharide (LPS) receptor revolutionized innate immunity. This finding revealed how the body senses bacterial endotoxins, opening new therapeutic avenues.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation.

Genes and immunity·2013

Same author

Massively parallel sequencing of the mouse exome to accurately identify rare, induced mutations: an immediate source for thousands of new mouse models.

Open biology·2012

Same author

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates.

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas·2009

Same author

The forward genetic dissection of afferent innate immunity.

Current topics in microbiology and immunology·2008

Same author

Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science, 1985, 229(4716):869-871. Classical article.

Journal of immunology (Baltimore, Md. : 1950)·2008

Same author

TLR signaling pathways: opportunities for activation and blockade in pursuit of therapy.

Current pharmaceutical design·2006

Area of Science:

Immunology
Molecular Biology
Genetics

Background:

The innate immune system's ability to detect endotoxin (lipopolysaccharide, LPS) is a long-standing observation.
The precise molecular mechanism for LPS-initiated signaling remained elusive for over a century.
The discovery of Toll-like receptors (TLRs) provided a framework for understanding innate immune pattern recognition.

Purpose of the Study:

To identify the molecular receptor responsible for sensing lipopolysaccharide (LPS).
To elucidate the mechanism of LPS signal initiation in the innate immune response.
To explore the evolutionary prevalence and therapeutic potential of the LPS sensing pathway.

Main Methods:

Positional cloning was employed to identify the LPS receptor.
Gene knockout studies were conducted to validate the function of Toll-like receptors (TLRs).

Main Results:

Toll-like receptor 4 (TLR4) was identified as the central component of the LPS receptor in 1998.
Subsequent gene knockout experiments confirmed that TLRs recognize conserved microbial molecular structures.
TLR4's specific LPS-sensing function is predominantly found in Mammalia, which exhibit high sensitivity to LPS.

Conclusions:

The identification of TLR4 as the LPS receptor provided a key insight into innate immunity.
The conserved nature of TLRs highlights their critical role in microbial recognition.
The singular biochemical pathway for LPS signaling presents significant pharmacotherapeutic opportunities.

Related Experiment Videos