IMMUNE RESPONSE TO HUMAN PATHOGENS EXPOSED TO SIMULATED MARS CONDITIONS – IMPLICATIONS TO HUMAN HEALTH ON MARS

Kurzfassung

Introduction: The increase in crewed space missions brings new challenges to take into consideration, especially related to crew health. Despite strict cleaning and sterilization techniques, inside the spacecraft assembly facilities (SAFs), the ISS and other spacecrafts, microorganisms from all 3 domains of life such as bacteria, fungi and archaea have been extensively isolated and identified. Particularly inside crew compartments, where astronauts live and work, the swabbing of surfaces has highlighted the presence of pathogenic bacteria and fungi. In addition, it has been shown that certain human-associated bacteria can survive to an extent on the Martian surface. Therefore, a possible infection of astronauts during a space mission, especially of long duration (e.g. a Mars mission), where food and medical supplies are scarce cannot be excluded as bacteria which are part of the human microbiome will be transported. Furthermore, the dysregulation of the immune system during space travel due to microgravity, radiation and limited nutrient diversity, could potentially exacerbate the effects of an infection. We therefore wanted to study the responses of the human immune system when exposed to pathogenic bacteria which have survived Mars-like conditions a situation which could take place during a long duration space mission to Mars. In this project, we evaluated the immune response of peripheral blood mononuclear cells (PBMCs) stimulated by Klebsiella pneumoniae and Serratia marcescens, two bacteria exposed to a range of Mars conditions including desiccation, sodium perchlorate exposure, UV radiation, Mars atmosphere and pressure. Evaluating the immune response to these bacteria could help with identifying treatments, and evaluate the risks for future long duration crewed missions. Methods: K. pneumoniae and S. marcescens were grown in minimal media supplemented with a single carbon source, D-gluconic acid. The bacteria were exposed to a combination of Mars simulated conditions including: desiccation, Mars atmosphere and pressure and polychromatic UV (200- 400 nm) radiation. PBMCs were stimulated with the selected bacteria and different parameter of immune effector function were measured (cytokine secretion, reactive oxygen species and phagocytosis) and transmission electron microscopy to evaluate bacterial cell state following exposure to the Mars-like conditions. Results: Cytokine quantification results show that there is a lower overall response of immune cells after stimulation with K. pneumoniae and S. marcescens exposed to Mars like-conditions. Desiccation is the condition which brings the biggest change in cytokine response, lowering cytokine production when PBMCs are stimulated with either microorganism. Polychromatic UV radiation and Mars atmosphere are the conditions which also show a lowered cytokine response. Interestingly K. pneumoniae is phagocytosed more, under all exposures, compared to exposed S. marcescens. ROS production is lower for both bacteria after being exposed to Mars conditions. Of interest is also the increased phagocytosis response of S. marcescens after being desiccated and re-grown, suggesting that the immune system could recognize the bacteria similarly after they are re-grown in the media comparatively to the control condition. Conclusions: The data indicate that the recognition of bacteria and the immune response would be affected by Mars-like conditions. In vivo studies are needed to understand the consequences in terms of infection severity. Furthermore, re-growing the bacteria in minimal media after desiccation revealed that the adaptations to Mars-like conditions could be reversible.