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Nature Medicine 10, 1173 - 1174 (2004)
doi:10.1038/nm1104-1173

From plankton to pathogen recognition

Robert L Modlin1,2 & Genhong Cheng2

  1. Division of Dermatology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095, USA. e-mail: rmodlin@mednet.ucla.edu
  2. Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095, USA.

Two studies in the mid-1990s cracked a mystery of innate immunity–how foreign invaders are recognized. One study found that signaling through Toll-like receptor 4 activated the immune response. Another identified the signal: lipopolysaccharide (LPS), a cell envelope component of Gram-negative bacteria. The discoveries brought full circle observations that began with starfish in the 1880s.

Our present understanding of microbial immunology is based on the seminal observations of Elie Metchnikoff, who by studying starfish larvae realized that mobile cells might serve in the host's defense against microbial invaders. In 1884, Metchnikoff published studies on the planktonic water-flea Daphnia magna (Fig. 1

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