Toll mediated infection response is altered by gravity and spaceflight in Drosophila.
Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immune-related conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response.
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
Katherine
K
Taylor
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
Kurt
K
Kleinhesselink
Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America.
Michael D
MD
George
Department of Biology, University of Central Florida, Orlando, Florida, United States of America.
Rachel
R
Morgan
Department of Biology, University of Central Florida, Orlando, Florida, United States of America.
Tangi
T
Smallwood
Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
Ann S
AS
Hammonds
Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, United States of America.
Patrick M
PM
Fuller
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
Perot
P
Saelao
Laverlam International, Butte, Montana, United States of America.
Jeff
J
Alley
School of Life Sciences, University of Nevada, Las Vegas, Nevada, United States of America.
Allen G
AG
Gibbs
School of Life Sciences, University of Nevada, Las Vegas, Nevada, United States of America.
Deborah K
DK
Hoshizaki
Department of Biology, University of Central Florida, Orlando, Florida, United States of America.
Laurence
L
von Kalm
Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, United States of America.
Charles A
CA
Fuller
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
Kathleen M
KM
Beckingham
Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
Deborah A
DA
Kimbrell
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D020171:Botrytis / Q000276:immunology*; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D018471:Hypergravity; D007113:Immunity, Innate; D016867:Immunocompromised Host; D008297:Male; D015398:Signal Transduction; D013026:Space Flight; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology; D014893:Weightlessness
D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D051193:Toll-Like Receptors; C530994:Yuri protein, Drosophila; C091227:DRS protein, Drosophila; C096696:Mtk protein, Drosophila