Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large

Bruce Beutler, Zhengfan Jiang, Philippe Georgel, Karine Crozat, Ben Croker, Sophie Rutschmann, Xin Du, Kasper Hoebe

Research output: Contribution to journalReview articlepeer-review

664 Scopus citations


Classical genetic methods, driven by phenotype rather than hypotheses, generally permit the identification of all proteins that serve nonredundant functions in a defined biological process. Long before this goal is achieved, and sometimes at the very outset, genetics may cut to the heart of a biological puzzle. So it was in the field of mammalian innate immunity. The positional cloning of a spontaneous mutation that caused lipopolysaccharide resistance and susceptibility to Gram-negative infection led directly to the understanding that Toll-like receptors (TLRs) are essential sensors of microbial infection. Other mutations, induced by the random germ line mutagen ENU (N-ethyl-N-nitrosourea), have disclosed key molecules in the TLR signaling pathways and helped us to construct a reasonably sophisticated portrait of the afferent innate immune response. A still broader genetic screen-one that detects all mutations that compromise survival during infection-is permitting fresh insight into the number and types of proteins that mammals use to defend themselves against microbes.

Original languageEnglish (US)
Pages (from-to)353-389
Number of pages37
JournalAnnual review of immunology
StatePublished - 2006


  • Infection
  • Innate immunity
  • Mendelian genetics
  • Mutagenesis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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