Back to Search
Start Over
Simulated microgravity suppresses MAPK pathway‐mediated innate immune response to bacterial infection and induces gut microbiota dysbiosis
- Source :
- The FASEB Journal. 34:14631-14644
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- During spaceflight, astronauts are subjected to various physical stressors including microgravity, which could cause immune dysfunction and thus potentially predispose astronauts to infections and illness. However, the mechanisms by which microgravity affects innate immunity remain largely unclear. In this study, we conducted RNA-sequencing analysis to show that simulated microgravity (SMG) suppresses the production of inflammatory cytokines including tumor necrosis factor (TNF) and interleukin-6 (IL-6) as well as the activation of the innate immune signaling pathways including the p38 mitogen-activated protein kinase (MAPK) and the Erk1/2 MAPK pathways in the Enteropathogenic escherichia coli (EPEC)-infected macrophage cells. We then adopted hindlimb-unloading (HU) mice, a model mimicking the microgravity of a spaceflight environment, to demonstrate that microgravity suppresses proinflammatory cytokine-mediated intestinal immunity to Citrobacter rodentium infection and induces the disturbance of gut microbiota, both of which phenotypes could be largely corrected by the introduction of VSL#3, a high-concentration probiotic preparation of eight live freeze-dried bacterial species. Taken together, our study provides new insights into microgravity-mediated innate immune suppression and intestinal microbiota disturbance, and suggests that probiotic VSL#3 has great potential as a dietary supplement in protecting individuals from spaceflight mission-associated infections and gut microbiota dysbiosis.
- Subjects :
- Male
0301 basic medicine
MAPK/ERK pathway
MAP Kinase Signaling System
Biology
Gut flora
Biochemistry
Proinflammatory cytokine
Enteropathogenic Escherichia coli
Mice
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Genetics
medicine
Animals
Macrophage
Intestinal Mucosa
Molecular Biology
Weightlessness Simulation
Innate immune system
Probiotics
medicine.disease
biology.organism_classification
Immunity, Innate
Gastrointestinal Microbiome
Mice, Inbred C57BL
030104 developmental biology
Immunology
Citrobacter rodentium
Dysbiosis
Female
Tumor necrosis factor alpha
Signal transduction
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....91206e48f03c6f153c70ccf263853495