FROM LEFT TO RIGHT: Beutler, Hoffmann and Steinman

Mosimann for Balzan, Rockefeller University Press

UPDATED: Pioneering Immunology Trio, Including One Who Died Days Ago, Shares Medicine Nobel

Three scientists who studied how the immune system kicks into action share this year's Nobel Prize in physiology or medicine.

One-half of the $1.45 million award is shared by Bruce Beutler of the Scripps Research Institute in San Diego, California, and Jules Hoffmann of the University of Strasbourg in France, who unraveled crucial details of how the innate immune system—the broad, first-line defense against microbial pathogens—is activated. The other half goes to Ralph Steinman of Rockefeller University in New York City, for his discovery of so-called dendritic cells and the role they play in the activation of T cells. The announcements were made this morning at 11:30 at a press conference in Stockholm (UPDATE: Rockefeller University has disclosed that Steinman died on 30 September; more on this below).

Hoffmann, who was born in Luxembourg but has spent his career in France and chaired the French Academy of Sciences, is rewarded for discovering that a gene called Toll—known to be involved in embryonal development—plays a key role in mounting an innate immune defense against bacteria and fungi in fruit flies; mutants without Toll died from such infections, he and his co-workers reported in a 1996 paper in Cell.

In a paper published in Science 2 years later, Beutler reported that a mutation in another gene similar to Toll—and dubbed a Toll-like receptor—played an important role in the innate immune system in mice. (Beutler was looking for the receptor that binds a bacterial compound called lipopolysaccharide, which can cause septic shock, a dangerous overreaction of the immune system that can be fatal.) "These findings showed that mammals and fruit flies use similar molecules to activate innate immunity when encountering pathogenic microorganisms," a press release by the Nobel foundation says. "The sensors of innate immunity had finally been discovered."

The discoveries quickly led to an explosion in research on TLRs. "It's marvelous that this area of immunology is recognized by the Nobel committee," says Douglas Fearon, an immunologist at the University of Cambridge who has explored connections between the innate immune response and the later, more specific adaptive immune response.

Steinman—who was born in Montreal and directed Rockefeller's Center for Immunology and Immune Diseases—worked on this adaptive side of the immune system, the arm that targets specific microbes with killer cells and antibodies. In 1973, he discovered a new cell type within the immune system that he dubbed dendritic cells; he later went on to show that they can activate the immune system's T cells to target specific microbes and helped unravel the mechanisms by which the adaptive immune system decides whether to mount a response.

Beutler, Steinman, and Hoffmann are "very good and obvious choices," says Rolf Zinkernagel, who shared the 1996 Nobel for his research on the development of adaptive immunity. "I'm happy about this prize. … Very often the detailed analysis [of immunology as a field] forgets this whole activity has one major goal: to combat infection in an animal."

At a ceremony in Hong Kong last week, Beutler and Hoffmann were also awarded the 2011 Shaw Prize in Life Science and Medicine, funded by media tycoon and philanthropist Run Run Shaw; they shared that award with Yale immunologist Ruslan Medzhitov. And on 22 September, France's National Center for Scientific Research (CNRS) announced that Hoffmann is the 2011 winner of the Gold Medal, the highest scientific honor in France.

Rockefeller University has just announced that Steinman passed away on 30 September after a 4-year battle with pancreatic cancer. ("His life was extended using a dendritic-cell-based immunotherapy of his own design," the university said.) Nobel prizes are normally only awarded to living scientists; Associated Press quoted Nobel committee member Goran Hansson as saying that the Nobel committee didn't know Steinman was dead when it chose him as a winner and was looking through its regulations.

Some past news coverage in Science related to this year's prize:

Targeting the Tolls (14 April 2006)

On the front lines of the body's defense against microbes, toll-like receptors are choice targets for drugs to combat infectious diseases and inflammation.

Fly Development Genes Lead to Immune Find (25 September 1998)

Over the past few years, researchers have found that a family of proteins related to the Toll protein of fruit flies, which was first identified as a developmental protein, plays a key role in triggering innate defenses against bacterial and fungal invaders—not only in flies, but in organisms as divergent as tobacco plants and humans.

Foiled Dendritic Cell Suicide May Lead to Autoimmunity (24 February 2006)

Dendritic cells activate lymphocytes to fight infection and then die by a form of cell suicide called apoptosis, possibly cutting the risk of an autoimmune attack. On page 1160, researchers report that blocking that apoptotic death in mice leads to dendritic cell buildup and the development of autoimmune symptoms.

And Action! Dendritic Cells Go Live (6 August 2004)

More than 7000 researchers gathered here from 18 to 23 July for the International Congress of Immunology and the Annual Conference of the Federation of Clinical Immunology Societies. Some of the most provocative news concerned dendritic cells.