Interleukin-22 promotes phagolysosomal fusion to induce protection against Salmonella enterica Typhimurium in human epithelial cells
| Autor: | Fernanda Schreiber, Matthias Zilbauer, Jessica L. Forbester, Judith Kraiczy, Eve L. Coomber, Subhankar Mukhopadhyay, David Goulding, Robert E. W. Hancock, Fiona Powrie, Trevor D. Lawley, Holm H. Uhlig, Sally Forrest, Amy T. Y. Yeung, Simon Clare, Gordon Dougan, Anneliese O. Speak, Emily A. Lees |
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| Přispěvatelé: | Speak, Anneliese [0000-0003-4890-4685], Kraiczy, Judith [0000-0001-9073-6318], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Salmonella typhimurium Salmonella Induced Pluripotent Stem Cells medicine.disease_cause Microbiology Transcriptome Interleukin 22 03 medical and health sciences 0302 clinical medicine Immune system Phagosomes medicine Humans Intestinal Mucosa Mutation Multidisciplinary biology interleukin-22 Interleukins Interleukin-21 Receptor alpha Subunit Epithelial Cells biology.organism_classification Interleukin-10 Receptor beta Subunit Phenotype Intestinal epithelium 030104 developmental biology Salmonella enterica intestinal organoids 030220 oncology & carcinogenesis Salmonella Infections |
| ISSN: | 0027-8424 |
| Popis: | Intestinal epithelial cells (IECs) play a key role in regulating immune responses and controlling infection. However, the direct role of IECs in restricting pathogens remains incompletely understood. Here, we provide evidence that IL-22 primed intestinal organoids derived from healthy human induced pluripotent stem cells (hIPSCs) to restrict Salmonella enterica serovar Typhimurium SL1344 infection. A combination of transcriptomics, bacterial invasion assays, and imaging suggests that IL-22–induced antimicrobial activity is driven by increased phagolysosomal fusion in IL-22–pretreated cells. The antimicrobial phenotype was absent in hIPSCs derived from a patient harboring a homozygous mutation in the IL10RB gene that inactivates the IL-22 receptor but was restored by genetically complementing the IL10RB deficiency. This study highlights a mechanism through which the IL-22 pathway facilitates the human intestinal epithelium to control microbial infection. |
| Databáze: | OpenAIRE |
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