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Innate immune cell response to host-parasite interaction in a human intestinal tissue microphysiological system
Mouhita Humayun1, Jose M Ayuso2,3,4, Keon Young Park5,6
1Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Science Advances
|May 11, 2022
Summary
A novel human intestinal model reveals how protozoan parasites like Toxoplasma gondii trigger immune responses. This system advances understanding of innate immunity and parasite control in humans.
Area of Science:
- Human immunology
- Parasitology
- Infectious disease modeling
Background:
- Protozoan parasites cause widespread human infections, ranging from mild to life-threatening, especially in immunocompromised individuals.
- Existing animal models offer limited insight into human innate immunity against parasites due to species-specific differences.
- There is a critical need for advanced in vitro systems to study human-parasite interactions and immune responses.
Purpose of the Study:
- To develop and utilize a human microphysiological system of intestinal tissue to investigate parasite-immune interactions.
- To elucidate the role of innate immune cells in epithelial infections caused by protozoan parasites, specifically Toxoplasma gondii.
- To explore mechanisms of immune control and parasite dissemination in a human-relevant in vitro setting.
Main Methods:
- Development of a human microphysiological system integrating primary intestinal epithelial cells and immune cells.
- Infection of the intestinal model with the protozoan parasite, Toxoplasma gondii.
- Analysis of effector functions and cytokine production by neutrophils and natural killer cells during infection.
Main Results:
- Epithelial infection by Toxoplasma gondii stimulated a broad range of effector functions in neutrophils.
- Natural killer cells exhibited parasite-specific cytokine production, indicating immunomodulatory roles.
- The developed system successfully modeled human-parasite interactions in the intestinal environment.
Conclusions:
- The human microphysiological system provides a valuable platform for studying innate immune responses to protozoan parasites.
- Neutrophils and natural killer cells play significant immunomodulatory roles during intestinal parasite infections.
- This system holds potential for advancing research on human-parasite interactions and developing therapeutic strategies.
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