Beutler thus discovered the key sensors of microbial infection in mammals. He found that one of the mammalian toll-like receptors, TLR4, acts as the membrane-spanning component of the mammalian LPS receptor complex. The TLRs work in the perception of microbes. Ten are now known in humans. Each detects signature molecules produced early in an infection. These receptors also work in severe illness, including shock and systemic inflammation as it occurs in the course of an infection. They are also active in sterile inflammatory and autoimmune diseases such as systemic lupus erythematosus. The research on TLRs won him the Nobel Prize in 2011.
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