Proceedings of the National Academy of Sciences of the United States of America · 2018
Interleukin-22 promotes phagolysosomal fusion to induce protection against Salmonella enterica Typhimurium in human epithelial cells.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Forbester Jessica L, Lees Emily A, Goulding David, Forrest Sally, Yeung Amy, Speak Anneliese, Clare Simon, Coomber Eve L, Mukhopadhyay Subhankar, Kraiczy Judith, Schreiber Fernanda, Lawley Trevor D, Hancock Robert E W, Uhlig Holm H, Zilbauer Matthias, Powrie Fiona, Dougan Gordon
Аннотация
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.