Abstract
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 language | English (US) |
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Pages (from-to) | 353-389 |
Number of pages | 37 |
Journal | Annual review of immunology |
Volume | 24 |
DOIs | |
State | Published - 2006 |
Keywords
- Infection
- Innate immunity
- Mendelian genetics
- Mutagenesis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology