title: Cell-cell propagation of NF-κB transcription factor and MAP kinase activation amplifies innate immunity against bacterial infection.
abstract: The enteroinvasive bacterium Shigella flexneri uses multiple secreted effector proteins to downregulate interleukin-8 (IL-8) expression in infected epithelial cells. Yet, massive IL-8 secretion is observed in Shigellosis. Here we report a host mechanism of cell-cell communication that circumvents the effector proteins and strongly amplifies IL-8 expression during bacterial infection. By monitoring proinflammatory signals at the single-cell level, we found that the activation of the transcription factor NF-κB and the MAP kinases JNK, ERK, and p38 rapidly propagated from infected to uninfected adjacent cells, leading to IL-8 production by uninfected bystander cells. Bystander IL-8 production was also observed during Listeria monocytogenes and Salmonella typhimurium infection. This response could be triggered by recognition of peptidoglycan and is mediated by gap junctions. Thus, we have identified a mechanism of cell-cell communication that amplifies innate immunity against bacterial infection by rapidly spreading proinflammatory signals via gap junctions to yet uninfected cells.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056, Basel, Switzerland.
authors.forename: Christoph Alexander
authors.initials: CA
authors.lastname: Kasper
authors.forename: Isabel
authors.initials: I
authors.lastname: Sorg
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmutz
authors.forename: Therese
authors.initials: T
authors.lastname: Tschon
authors.forename: Harry
authors.initials: H
authors.lastname: Wischnewski
authors.forename: Man Lyang
authors.initials: ML
authors.lastname: Kim
authors.forename: Cécile
authors.initials: C
authors.lastname: Arrieumerlou
mesh_terms: D018938:Caco-2 Cells; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D004405:Dysentery, Bacillary / Q000201:enzymology / Q000276:immunology*; D017629:Gap Junctions / Q000276:immunology / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000032:analysis / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology; D012763:Shigella flexneri / Q000201:enzymology / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D010457:Peptidoglycan; D020928:Mitogen-Activated Protein Kinases