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Toll-like receptors: Roles in disease and therapy

Francisco A Bonilla, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Anna M Feldweg, MD


The toll-like receptors (TLRs) are surface molecules on eukaryotic cells that detect and respond to microbial antigens. TLRs derive their name from homology to the Drosophila Toll molecule, an important component of an antifungal defense mechanism [1,2]. TLRs constitute a phylogenetically ancient system present in invertebrates and conserved through vertebrate evolution.

TLRs belong to a class of molecules known as pattern recognition receptors. The ligands for these receptors are components of pathogenic microbes and are often called pathogen-associated molecular patterns (PAMPs).

TLRs are frequently referred to as a system of nonspecific or "innate" immune defense (ie, the response is present and unchanging during the life of the organism and occurs in the same manner with every exposure to the pathogen) [3]. This is in contrast to specific or "adaptive" immunity (present only in vertebrates and mediated by lymphocytes), whereby the immune system response changes during the life of the host. Adaptive immune responses may be more vigorous (or suppressed) with each exposure to a pathogen depending upon encounters with that organism or others, and other conditions prevailing in the host. In vertebrates, although TLRs initiate protective functions that operate independently from adaptive immunity, they also modulate mechanisms having profound impact on the development of specific immune responses.

Innate immunity is reviewed separately. (See "An overview of the innate immune system" and "Immunity of the newborn".)


Different species have different numbers of distinct toll-like receptors (TLRs). At least 10 have been discovered in humans (TLR1-10) [1,2,4]. With the exception of TLR2, TLRs initiate signaling by homodimerization (eg, two identical TLRs brought together). TLR2 forms heterodimers with TLR1 or TLR6. Receptor structure/organization, ligands, and signaling are summarized in the table (table 1) and figure (figure 1).


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Literature review current through: Sep 2016. | This topic last updated: Mar 20, 2015.
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