Task Progress:
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Over the past 50 years, microorganisms have displayed unexpected responses relevant to infectious disease when grown in microgravity (and microgravity analogues), including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, and virulence. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system, consisting of altered leukocyte distribution, reductions in T and Natural Killer (NK) cell function, altered cytokine profiles, and reactivation of latent herpesviruses. Further, astronauts have some degree of clinical incidence, primarily infectious disease episodes and atopic dermatitis. The impact of microgravity on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized.
The goal of this study is to use spaceflight analogue conditions to define the relationship between altered virulence of medically-significant microorganisms aboard the International Space Station (ISS) and the immune response of the host, including astronaut immune cells. This information will provide critical understanding into the impact of microgravity on potential alterations of microbial virulence and associated infectious disease risk to crew health during spaceflight missions.
Specific Aims: Aim 1: Profile the synergistic relationship between spaceflight analogue-altered bacterial virulence characteristics and spaceflight analogue-altered immune cell function. Alterations in immune cell responses will be evaluated when human primary immune cells are challenged with pathogens in normal and spaceflight analogue growth conditions. Aim 2: Profile antimicrobial efficacy for astronauts participating in spaceflight via challenge with spaceflight analogue cultured bacterial pathogens. Primary immune cells from astronauts will be profiled before, during, and post-flight to identify alterations in host response to pathogens in normal and spaceflight analogue conditions.
This will be the first study to apply an integrated systematic approach to understand the relationship between spaceflight, immune cell function, and infectious disease risk for the crew. The results from this study will enhance the current infectious disease risk assessment for the crew, elucidate the relationship to clinical disease, and support future development and application of effective countermeasures for treatment and prevention.
In 2021, Immunology and Microbiology laboratory personnel worked diligently to optimize the culture conditions and flow cytometry panels prior to beginning work on crew samples. This included several trial runs testing different microbial growth conditions, cellular surface markers, and preparations for analysis by confocal and fluorescent microscopy. The trial runs included testing of 4 bacteria: Burkholderia cepacia, Salmonella enteritidis, Pseudomonas aeruginosa, and Enterohemorrhagic E. coli. The bacteria were cultured with both whole blood and peripheral blood mononuclear cells.
The IRB (Institutional Review Board) protocol for this study was submitted and approved in March 2020. Informed consent briefings for crew members began in December 2020. To date, five crew members have enrolled in this study and the first two sample collections (L-180 and L-90) have occurred for two of those individuals. Additionally, two crew members are scheduled for their first sample collection (L-180) in early October 2021.
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