Linh Pham

Glowing sicker.
Bacteria expressing a green fluorescence protein have infected the whole fly, even spreading out into its wings.

An Infection to Remember

Immunology textbooks may be in need of a rewrite. The hallmark of vertebrate immune systems is their ability to "remember" an infection and mount specific attacks against microbial invaders the next time they come knocking. But a new study of fruit flies adds to the growing suspicion that invertebrates are capable of something quite similar, suggesting that even relatively simple immune systems can act in ways immunologists never thought possible.

The vertebrate immune system has two parts: innate and adaptive immunity. All animals are born with innate immunity, general defenses that react to all potential threats the same way. Examples include immune cells called phagocytes, which devour any unwanted foreigners in the body's tissues. Beyond these simple defenses, vertebrates have evolved adaptive immunity--an intricate mix of immune cells that recognize specific invaders and target repeat offenders.

In recent years, the invertebrate immune system has shown signs that it may be more complex than immunologists have given it credit for. Studies have shown, for example, that cockroaches and bumblebees develop long-term protection against certain microbes--although biologists aren't sure how this happens. And work in fruit flies indicates that they can subtly alter their immune cells to deal with different types of microbes (ScienceNOW, 18 August 2005).

Now comes a more compelling example. Graduate student Linh Pham and David Schneider, a biologist at Stanford University, took another look at fruit flies. Through a series of experiments that required nearly a million flies, Pham found that she could essentially vaccinate the insects against Streptococcus pneumoniae, bacteria that can cause pneumonia in people. First, she injected flies with a nonlethal dose of the bacteria. A week later, she re-injected the flies with normally lethal doses of S. pneumoniae. Instead of dying, the flies survived just as long as control flies that weren't infected. In a subsequent experiment, Pham showed this immune response was specific to S. pneumoniae, as the vaccinated flies couldn't survive lethal doses of other types of microbes. What's more, the flies retained this immunity for the rest of their lives, Pham and her colleagues report today in PLoS Pathogens. When the team shut down the flies' phagocytes, they were no longer protected from the bacteria, implicating these cells in the flies' adaptivelike immune response.

This work is "very, very exciting," says Dietmar Schmucker, a molecular biologist at the Harvard Medical School in Boston, Massachusetts. Understanding how the insect immune system works, he notes, could help us figure out how bugs carry and transmit human disease without getting sick themselves. Richard Karp, an immunologist at the University of Cincinnati in Ohio, agrees that this is "an intriguing piece of work," but cautions that there are "lots of loose ends to pull together," such as how phagocytes can develop specificity against particular microbes.

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