2006/03/21 by Bruce Beutler, Zhengfan Jiang, Philippe Georgel +5 · 1 citation
Immunology and Microbiology · #Immune Response and Inflammation #Antimicrobial Peptides and Activities #interferon and immune responses
paper · doi:10.1146/annurev.immunol.24.021605.090552
openalex publication_date 2006/03/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
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.