Infections have evolved ways to invade host cells and cause disease. The physical forces that impact host-pathogen interactions and disease outcomes have often been overlooked by researchers.
The authors of the new study show that under low fluid shear force conditions that mimic those found in microgravity culture during spaceflight, the foodborne pathogen Salmonella can cause unique alterations to 3D models of human intestinal tissue.
Previous work by the same team shows that the physical forces of fluid shear acting on both the pathogen and host can change the landscape of infections.
Ensuring the health of astronauts on extended space missions is dependent on understanding the interplay of host and pathogen. Low fluid shear forces are found in certain tissues in our bodies that can be used to transmit diseases, and this research sheds new light on the mysterious processes of infection on earth.
This is the first time that S. Typhimurium has been grown in a shake flask under low fluid shear conditions.
The 3D co-culture intestinal model used in this study is more accurate in replicating the structure and behavior of the same tissue within the human body and is more indicative of responses to infections.
There were dramatic changes in the expression of genes in 3D intestinal cells after they were 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 800-273-3217 Many of the changes occurred in genes that are involved in S. Typhimurium's ability to invade and colonize host cells.
The lack of a comprehensive understanding of the impact of space travel on crew health is a major challenge limiting human exploration of space. Understanding the relationship between spaceflight, immune cell function, and microorganisms will be essential to understand infectious disease risk for humans, since microbes accompany humans wherever they travel and are essential for controlling the balance between health and disease.
The new study was co- directed by Nickerson and Barrila, who are both professors at the School of Life Sciences at Arizona State University. The current issue of the journal contains the research.
Life-changing force.
Under wildly different environmental conditions, life on earth has diversified into an almost incomprehensibly vast array of forms. One of the parameters has remained constant. All living organisms evolved under and respond to the pull of Earth's gravity.
For more than 20 years, Nickerson has been a pioneer in exploring the effects of the reduced microgravity environment of spaceflight on a range of pathogenic microbes and the impact on interactions with human cells and animals. She and her colleagues have pursued this research in both land-based and spaceflight settings, the results of which helped lay the foundation for the rapidly growing research field, mechanobiology of infectious disease, the study of how physical forces impact infection and disease outcomes.
They found that the low fluid shear conditions associated with spaceflight and spaceflight analog culture are similar to those encountered by pathogens inside the host, and that these conditions can induce unique changes in the ability of pathogens to aggressively attack host cells.
The new study looked at the infectious agent that causes gastrointestinal disease in humans and animals. Food-borne illness is the leading cause of death in the United States. About 1.35 million infections, 26,500 hospitalizations, and 420 deaths are caused by the disease, according to the CDC. Most of the illnesses are caused by contaminated foods.
After an outbreak of the disease, it can take 6 hours to 6 days for the symptoms to go away. Illness from the disease can last up to 7 days. In severe cases, hospitalization may be required.
Shear chance?
The cells in mammals are exposed to the fluid flowing over their outer surfaces. The force of fluid gliding over cell surfaces can cause changes to affected cells, just as a gentle downstream current will affect the pebbles in the underlying streambed differently than a raging torrent. It is called fluid shear because of the liquid abrasion of cell surfaces.
Since spaceflight experiments are rare and access to the space research platform is limited, researchers often use a rotating wall vessel bioreactor to grow cells in liquid growth media in a simulation of the low fluid shear conditions encountered during culture in spaceflight. Cells are maintained in suspension as the reactor rotates, tumbling in their culture medium. The process mimics the low fluid shear conditions that cells experience in spaceflight.
The team has shown that the fluid shear level is relevant to conditions in the human intestine and other tissues where the immune system is trying to destroy the cells.
A portrait of an individual.
The study found changes in the expression of genes and the ability to cause infections in 3D models. Two strains of S. Typhimurium were involved in the experiments.
Hfq is a major stress response regulator in Salmonella, but the wild strain did not have it. Nickerson and her team discovered that Hfq acts as a master regulator of the infection process in spaceflight and spaceflight analog culture. Hfq is used by additional pathogens to regulate their responses to the same conditions.
The hfq Mutant strain was able to survive within 3D tissue models at levels comparable to the wild type strain. Despite the removal of Hfq, many genes associated with cell adherence, motility, and invasion were still active in the mutant strain.
The model responded to the infections by upregulating genes involved in inflammation, tissue remodeling, and wound healing, when it was grown under microgravity conditions. This was observed for both wild and hfq strains of the pathogen.
The data from this new spaceflight analog study supports previous findings. The 2010 flight experiment aboard Space Shuttle Discovery used the same wild type strain of S. Typhimurium that was used in the new study.
In the new spaceflight analog study, there were several similarities between host cell responses to infections and those reported during the STL-IMMUNE experiment. The results reinforce the RWV as a ground-based spaceflight culture analogue system that mimics key aspects of spaceflight culture.
The key genes and proteomic biosignatures that were consistent with enhanced infections by the pathogen were discovered by Barrila. The use of the RWV bioreactor as a spaceflight analog culture system in our current study has allowed us to explore this experimental question at a deeper level.
New experiences.
There is a double risk from infectious disease for astronauts. Their immune systems are weakened by the combined rigors of spaceflight. Microgravity may cause some pathogens to become more effective infectious agents by triggering low fluid shear conditions.
With longer spaceflight missions in the advanced planning stages and the advent of civilian space travel rapidly emerging, it's vital to safeguard space travelers from infectious disease.
Studies like the current one are helping to pull back the curtain on the infection process, which is relevant to the battle against diseases on Earth and beyond.
More information: Spaceflight analogue culture enhances the host-pathogen interaction between salmonella and a 3-D biomimetic intestinal co-culture model, Frontiers in Cellular and Infection Microbiology (2022). DOI: 10.3389/fcimb.2022.705647
All Rights Reserved © 2024
