Space-raised flies show weakened immunity to fungus

It's well established that spaceflight affects immune responses, said Deborah Kimbrell, a researcher in the Department of Molecular and Cellular Biology in the UC Davis College of Biological Sciences, who led the study. Drosophila share many fundamentals of the immune system with mammals such as mice and humans. With funding from NASA, Kimbrell and colleagues initiated the first study of Drosophila immunity and gravity, using first hypergravity (increased gravity), and then microgravity, the decreased gravity of spaceflight.

The flies were sent into space as eggs on a 12-day mission aboard the Space Shuttle Discovery. The flies take about 10 days to develop into adults. After they returned to Earth, Kimbrell and colleagues tested their responses to two different infections: a fungus, which flies fight off through a pathway mediated by the Toll receptor, and a bacterial infection that flies resist through a gene called Imd ("immune deficiency").

Both the Toll and Imd pathways have counterparts in humans and other mammals: The 2011 Nobel Prize in physiology and medicine was awarded for discovery of Toll receptor activation of innate immunity in flies and mammals.

While the response through the Imd pathway was robust, the Toll pathway was "non-functional" in space-raised flies, Kimbrell said.

In Earth-based experiments, the researchers found that when flies were tested in a centrifuge under hypergravity conditions, their resistance to the fungus was improved, suggesting that their Toll pathway was boosted. However, for the mutant yuri gagarin, which lacks normal responses to gravitational fields, resistance was the same at normal and hypergravity, further demonstrating a link between gravity and the immune response.

Future spacecraft designed for long missions could already include centrifuges that crew could use to keep up bone and muscle mass: it turns out that this might also have a beneficial effect on astronauts' immune systems, Kimbrell said.

How does microgravity affect the immune system? Kimbrell said they have two hypotheses in mind, which are testable both in humans and flies.

Firstly, the space flies also showed high expression of genes for heat-shock proteins, which are produced in response to physiological stress. Heat shock proteins bind directly with mammalian Toll receptors, Kimbrell said, and may also moderate Toll activation in Drosophila. Another possibility is that microgravity interferes with the behavior of proteins outside the cell -- an area that is more important for Toll than for Imd signaling, she said.

The team hopes to carry out future research with flies on the International Space Station.

Kimbrell's co-authors on the paper were: at UC Davis, Katherine Taylor, Kurt Kleinhesselink, and Perot Saelao, Department of Molecular and Cellular Biology; Michael George, Department of Medical Microbiology and Immunology; Charles Fuller and Patrick Fuller, Department of Neurobiology, Physiology and Behavior; Rachel Morgan, Tangi Smallwood, Laurence von Kalm, University of Central Florida; Ann Hammonds, Lawrence Berkeley National Laboratory; Jeff Alley, Laverlam International, Butte, Montana; Allen Gibbs and Deborah Hoshizaki, University of Nevada, Las Vegas; and Kathleen Beckingham, Rice University.