Spaceflight: Microgravity analog culture profoundly affects microbial infection process in 3-D human tissue models

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 3-D models of human intestinal tissue at much higher levels, and induces unique alterations in gene expression.

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 3-D intestinal models, this study marks the first time that S. Typhimurium has been grown under the low fluid shear conditions of simulated microgravity and then used to infect a 3-D model of human intestinal epithelium co-cultured with macrophage immune cells, key cell types targeted by Salmonella during infection.

The 3-D 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.

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