Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [3];  [3];  [4];  [2];  [2];  [5];  [6];  [6];  [3];  [2];  [7];  [2]
  1. University of California, Davis, CA (United States); DOE/OSTI
  2. University of California, Davis, CA (United States)
  3. University of Central Florida, Orlando, FL (United States)
  4. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
  5. Laverlam International, Butte, MT (United States)
  6. University of Nevada, Las Vegas, NV (United States)
  7. Rice University, Houston, TX (United States)

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 immunerelated 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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Aeronautics and Space Administration (NASA)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1627673
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 1 Vol. 9; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (64)

The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll ‐pathway activation function journal April 2010
A Family of Turandot-Related Genes in the Humoral Stress Response of Drosophila journal June 2001
Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin journal May 1998
Immune System Dysregulation Occurs During Short Duration Spaceflight On Board the Space Shuttle journal October 2012
Toll-like receptors journal July 2011
Characterization of Drosophila melanogaster cytochrome P450 genes journal March 2009
Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity journal May 2000
Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays journal October 2001
The Drosophila SUN protein Spag4 cooperates with the coiled-coil protein Yuri Gagarin to maintain association of the basal body and spermatid nucleus journal August 2010
The Drosophila Toll Signaling Pathway journal January 2011
Host Immune Response and Differential Survival of the Sexes in Drosophila journal July 2007
Regulation of heat shock protein message in Jurkat cells cultured under serum-starved and gravity-altered conditions journal April 2000
Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis journal November 2010
Changes in gravitational force cause changes in gene expression in the lens of developing zebrafish journal August 2006
Measurement of protein using bicinchoninic acid journal October 1985
The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults journal September 1996
Signaling Role of Hemocytes in Drosophila JAK/STAT-Dependent Response to Septic Injury journal September 2003
Heat-shock proteins can promote as well as regulate autoimmunity journal March 2009
Dual Detection of Fungal Infections in Drosophila via Recognition of Glucans and Sensing of Virulence Factors journal December 2006
Chaperone-Assisted Selective Autophagy Is Essential for Muscle Maintenance journal January 2010
The Drosophila clotting system and its messages for mammals journal January 2014
Conventional and non-conventional Drosophila Toll signaling journal January 2014
Dynamic Coordination of Innate Immune Signaling and Insulin Signaling Regulates Systemic Responses to Localized DNA Damage journal June 2011
Virus Recognition by Toll-7 Activates Antiviral Autophagy in Drosophila journal April 2012
The Heat Shock Response: Life on the Verge of Death journal October 2010
Tropomyosin is an interaction partner of the Drosophila coiled coil protein Yuri Gagarin journal February 2011
Genetic evidence of a redox-dependent systemic wound response via Hayan Protease-Phenoloxidase system in Drosophila: Redox-modulated systemic wound response journal January 2012
Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll journal August 2008
Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq journal September 2007
Endocytic pathway is required for Drosophila Toll innate immune signaling journal April 2010
Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway journal May 2001
ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila journal February 2012
A genome-wide analysis of immune responses in Drosophila journal December 2001
Characterization of the DrosophilaCaspase, DAMM journal January 2001
Two Proteases Defining a Melanization Cascade in the Immune System of Drosophila journal July 2006
The Toll and Imd pathways are the major regulators of the immune response in Drosophila journal June 2002
FlyBase: improvements to the bibliography journal November 2012
Transcriptional regulation of xenobiotic detoxification in Drosophila journal September 2011
Crystallization and preliminary X-ray crystallographic studies of Drep-3, a DFF-related protein from Drosophila melanogaster journal May 2006
The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila journal April 2006
Gravitaxis in Drosophila melanogaster: a forward genetic screen journal April 2006
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein journal March 2002
Stressed to Death: Regulation of Apoptotic Signaling Pathways by the Heat Shock Proteins journal July 2001
Heightened Cytotoxic Responses and Impaired Biogenesis Contribute to Early Pathogenesis in the Oral Mucosa of Simian Immunodeficiency Virus-Infected Rhesus Macaques journal December 2008
The Host Defense of Drosophila melanogaster journal April 2007
Analysis of Thioester-Containing Proteins during the Innate Immune Response of Drosophila melanogaster journal November 2010
Immune Response in the Barrier Epithelia: Lessons from the Fruit Fly Drosophila melanogaster journal January 2012
Effects of microgravity and hypergravity on platelet functions journal January 2009
Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster journal January 2012
Signal transduction in cells of the immune system in microgravity journal October 2008
Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth's orbit? journal August 2009
The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity journal December 2012
yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis journal June 2008
Signalling through mechanical inputs – a coordinated process journal July 2012
Mechanisms Underlying Hypoxia Tolerance in Drosophila melanogaster: hairy as a Metabolic Switch journal October 2008
Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight journal January 2011
Toll-8/Tollo Negatively Regulates Antimicrobial Response in the Drosophila Respiratory Epithelium journal October 2011
Age-Specific Variation in Immune Response in Drosophila melanogaster Has a Genetic Basis journal July 2012
The Immune System in Space, Including Earth-Based Benefits of Space- Based Research journal August 2005
Extracellular Heat Shock Proteins: Alarmins for the Host Immune System journal October 2011
Heat Shock Proteins: Conditional Mediators of Inflammation in Tumor Immunity journal January 2012
Spaceflight engages heat shock protein and other molecular chaperone genes in tissue culture cells of Arabidopsis thaliana journal January 2013
Regulation and function of the melanization reaction in Drosophila journal January 2009
Gut-associated microbes of Drosophila melanogaster journal July 2012

Cited By (2)

IL-6 and the dysregulation of immune, bone, muscle, and metabolic homeostasis during spaceflight journal December 2018
Near-optimal probabilistic RNA-seq quantification journal April 2016

Similar Records

Unexpected role of the IMD pathway in Drosophila gut defense against Staphylococcus aureus
Journal Article · Sun Jan 14 23:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23134074

Relevance of the Unfolded Protein Response to Spaceflight-Induced Transcriptional Reprogramming in Arabidopsis
Journal Article · Mon Dec 14 23:00:00 EST 2020 · Astrobiology · OSTI ID:1764378

Characterization of Spz5 as a novel ligand for Drosophila Toll-1 receptor
Journal Article · Wed Nov 14 23:00:00 EST 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23125263