Exploring host-commensal-pathogen dynamics in cell line and organotypic human intestinal epithelial models
Nening M. Nanlohy,
Nina Johannesson,
Lucas Wijnands,
Laura Arroyo,
Jelle de Wit,
Gerco den Hartog,
Katja C. Wolthers,
Adithya Sridhar,
Susana Fuentes
Affiliations
Nening M. Nanlohy
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Nina Johannesson
OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; OrganoVIR Labs, Department of Pediatric Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
Lucas Wijnands
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Laura Arroyo
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Jelle de Wit
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Gerco den Hartog
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Laboratory of Medical Immunology, Radboudumc, Nijmegen, the Netherlands
Katja C. Wolthers
OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
Adithya Sridhar
OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC, Location AMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; OrganoVIR Labs, Department of Pediatric Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, The Netherlands
Susana Fuentes
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Corresponding author
Summary: Host and microbiome intricately interact in the ecosystem of the human digestive tract, playing a crucial role in our health. These interactions can initiate immune responses in the epithelial cells, which, in turn, activate downstream responses in other immune cells. Here, we used a CaCo-2 and a human intestinal enteroid (HIE) model to explore epithelial responses to both commensal and pathogenic bacteria, individually and combined. CaCo-2 cells were co-cultured with peripheral blood mononuclear cells, revealing downstream activation of immune cells. While both systems showed comparable cytokine profiles, they differed in their responses to the different bacteria, with the organoid system being more representative of responses observed in humans. We provide evidence of the pro-inflammatory responses associated with these bacteria. These models contribute to a deeper understanding of the interactions between the microbiota, intestinal epithelium, and immune cells in the gut, promoting advances in the field of host-microbe interactions.
