RT Journal Article SR Electronic T1 Innate immune cell response to host-parasite interaction in a human intestinal tissue microphysiological system JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.01.27.478058 DO 10.1101/2022.01.27.478058 A1 Mouhita Humayun A1 Jose M Ayuso A1 Keon Young Park A1 Bruno Martorelli Di Genova A1 Melissa Skala A1 Sheena C Kerr A1 Laura J. Knoll A1 David J. Beebe YR 2022 UL http://biorxiv.org/content/early/2022/01/28/2022.01.27.478058.abstract AB Protozoan parasites that infect humans are widespread, and lead to varied clinical manifestations, including life-threatening illnesses in immunocompromised individuals. Animal models have provided insight into innate immunity against parasitic infections, however, species-specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for novel in vitro systems that can elucidate mechanisms of immune control and parasite dissemination. We have developed a human microphysiological system of intestinal tissue to evaluate parasite-immune-specific interactions during infection, which integrates primary intestinal epithelial cells and immune cells to investigate the role of innate immune cells during epithelial infection by the protozoan parasite, Toxoplasma gondii, which affects billions of people worldwide. Our data indicate that epithelial-infection by parasites stimulates a broad range of effector functions in neutrophils and NK cell-mediated cytokine production that play immunomodulatory roles, demonstrating the potential of our system for advancing the study of human-parasite interactions.Teaser Novel engineered model of human intestinal tissue for study of dissemination and immune control of parasitic infections.Competing Interest StatementD.J.B. holds equity in BellBrook Labs LLC, Tasso Inc., Stacks to the Future LLC, Lynx Biosciences LLC, Onexio Biosystems LLC, Turba LLC, Flambeau Diagnostics LLC, and Salus Discovery LLC. D.J.B. is a consultant for Abbott Laboratories.