|In 1985, Christiane Nüsslein-Volhard discovered a set of genes that established Drosophila fruit fly embryonic development and dorsal-ventral axis. Nüsslein-Volhard exclaimed “Das ist ja Toll!” upon her discovery, which roughly translates from German to ‘That is amazing’ or ‘That is great!’ The Toll gene bore a resemblance to the IL-1 Receptor, the receptor for a potent pyrogen. Scientists then began to wonder whether Toll was involved with innate immunity. In 1996, Bruno Lemaitre et al. showed that Toll-deficient flies succumbed to fungal infection. Since then, Toll-Like Receptors (TLRs) have been discovered in mammals (fish, frogs, and invertebrates have their own specific TLRs and even plants and bacteria contain basic building blocks resembling TLR defenses).
TLRs play a vital role in innate immunity and are expressed on a variety of cell types. These proteins are known as pattern recognition receptors and help detect bacteria, fungi, protozoa, and viruses. TLR activation leads to a wide range of effects, including inflammation, complement activation, and phagocytosis.
It should be noted that the study of TLR expression has been difficult for several reasons: First, TLR detection is typically based on mRNA expression, due to limitations of available antibodies. Second, TLR gene expression does not necessarily guarantee responsiveness to its corresponding ligands. Third, TLR analysis can be further complicated if the ‘purified’ cells contain contaminating populations. Despite these limitations, it is vitally important to understand TLR expression and the role they play as an innate defense mechanism against microbial threats.