Potentiation of epithelial innate host responses by intercellular communication.
The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox) 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection.
Hannover Medical School, Hannover, Germany.
Tamas
T
Dolowschiak
Cécilia
C
Chassin
Sanae
S
Ben Mkaddem
Thilo M
TM
Fuchs
Siegfried
S
Weiss
Alain
A
Vandewalle
Mathias W
MW
Hornef
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism; D007113:Immunity, Innate; D015151:Immunoblotting; D047468:Immunoprecipitation; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001427:Bacterial Toxins; D016207:Cytokines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C038705:hlyA protein, Listeria monocytogenes