Abstract
While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground. Increased virulence was also observed in bacteria that were grown in simulated microgravity conditions on the ground using the rotating wall vessel. Increased virulence of the space-flown bacteria was similar in magnitude between wild-type flies and those that were mutants for the well-characterized immune pathways Imd and Toll, suggesting that changes to the host immune system after infection are likely not a major factor contributing towards increased susceptibility of ground-reared flies infected with space-flown bacteria. Characterization of the bacteria shows that at later timepoints spaceflight bacteria grew at a greater rate than ground controls in vitro, and in the host. These results suggest complex physiological changes occurring in pathogenic bacteria in space environments, and there may be novel mechanisms mediating these physiological effects that need to be characterized.
Highlights
As space exploration extends beyond low Earth orbit, there is considerable interest in understanding the changes in human physiology under spaceflight conditions
Host survival after injection of first ground subculture of spaceflight sample Given that two separate isolates of bacteria had shown increased virulence after spaceflight exposure (Fig. 1), we wanted to assess whether these changes were reversible physiological changes in the bacteria induced by the stress of spaceflight or whether they were genetically heritable changes induced, for instance, by ionizing radiation exposure during spaceflight
We found that flies infected with a bacterial pathogen that had been grown during spaceflight was significantly more lethal than ground controls (Fig. 1)
Summary
As space exploration extends beyond low Earth orbit, there is considerable interest in understanding the changes in human physiology under spaceflight conditions. Previous studies have demonstrated that these stressors have a significant impact on the ability of the immune system to respond appropriately to disease, including altered cytokine production,[1,2,3,4,5] changes in immune cell proliferation and distribution[4,6,7] and general alteration of immune homeostasis in both innate and adaptive immune systems.[8,9] This apparent immune dysregulation is even more important when considering that there have been studies demonstrating significant effects of microgravity and spaceflight conditions on the pathogens that co-occur with humans in space habitats.[10,11,12,13,14,15,16,17]. The fruit fly (Drosophila melanogaster) is a promising model for understanding the effects of spaceflight on human immunity and pathogenesis, as they have been shown previously to experience a dramatic shift in immune gene expression following spaceflight.[23,24] Using invertebrate models for investigating the human immune system has proven both fruitful and convenient, as they are cost-effective, have short generation times, and importantly, have immune systems with high homology to humans.[25,26] While invertebrates lack a characterized adaptive immune system, the inducible innate immune response of Drosophila melanogaster is highly similar to humans,[25,27,28] with about 75% of human disease-causing genes with a functional homolog in the fruit fly.[25,29]
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