New study provides essential insights into infectious disease risk during spaceflight
Researchers found microgravity analog culture profoundly affects microbial infection process in 3D human tissue models
June 1, 2022—Infectious microbes have evolved sophisticated means to invade host cells, outwit the body’s defenses and cause disease. While researchers have tried to puzzle out the complicated interactions between microorganisms and the host cells they infect, one facet of the disease process has often been overlooked – the physical forces that impact host-pathogen interactions and disease outcomes.
In a new study, corresponding authors Cheryl Nickerson, Jennifer Barrila and their colleagues demonstrate that under low-fluid, shear-force conditions that simulate those found in microgravity culture during spaceflight, the foodborne pathogen salmonella infects 3D models of human intestinal tissue at much higher levels and induces unique alterations in gene expression.
Image of salmonella bacteria set against an illustration of the 3D tissue model used in the study.
Graphic by drmicrobe
This study advances previous work by the same team showing that physical forces of fluid shear acting on both the pathogen and host can transform the landscape of infection.
Understanding this subtle interplay of host and pathogen during infection is critical to ensuring astronaut health, particularly on extended space missions. Such research also sheds new light on the still largely mysterious processes of infection on Earth, as low-fluid shear forces are also found in certain tissues in our bodies that pathogens infect, including the intestinal tract.
While the team has extensively characterized the interaction between conventionally grown shake-flask cultures of salmonella typhimurium and 3D intestinal models, this study marks the first time that salmonella typhimurium has been grown under the low-fluid shear conditions of simulated microgravity and then used to infect a 3D model of human intestinal epithelium co-cultured with macrophage immune cells, key cell types targeted by salmonella during infection.
The 3D co-culture intestinal model used in this study more faithfully replicates the structure and behavior of the same tissue within the human body and is more predictive of responses to infection, as compared with conventional laboratory cell cultures.
Results showed dramatic changes in gene expression of 3D intestinal cells following infection with both wild-type and mutant salmonella typhimurium strains grown under simulated microgravity conditions. Many of these changes occurred in genes known to be intimately involved with salmonella typhimurium’s prodigious ability to invade and colonize host cells and escape surveillance and destruction by the host’s immune system.
“A major challenge limiting human exploration of space is the lack of a comprehensive understanding of the impact of space travel on crew health,” Nickerson says. “This challenge will negatively impact both deep-space exploration by professional astronauts, as well as civilians participating in the rapidly expanding commercial space market in low Earth orbit. Since microbes accompany humans wherever they travel and are essential for controlling the balance between health and disease, understanding the relationship between spaceflight, immune cell function and microorganisms will be essential to understand infectious disease risk for humans.”
Nickerson, who co-directed the new study with Barrila, is a researcher in the Biodesign Center for Fundamental and Applied Microbiomics and is also a professor with ASU’s School of Life Sciences. Barrila is an assistant research professor with the Biodesign Center for Fundamental and Applied Microbiomics.
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Source: https://news.asu.edu/20220601-microgravity-analog-culture-profoundly-affects-microbial-infection-process-3d-human-tissue
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