Cell-Cell Propagation of NF-κB Transcription Factor and MAP Kinase Activation Amplifies Innate Immunity against Bacterial Infection

• Published in: Immunity (Cambridge, Mass.) Vol. 33; no. 5; pp. 804 - 816
• Main Authors: Kasper, Christoph Alexander, Sorg, Isabel, Schmutz, Christoph, Tschon, Therese, Wischnewski, Harry, Kim, Man Lyang, Arrieumerlou, Cécile
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.11.2010; Elsevier
• Subjects: Bacteria; Caco-2 Cells; Cell Communication - immunology; Cell Proliferation; Dysentery, Bacillary - enzymology; Dysentery, Bacillary - immunology; Gap Junctions - immunology; Gap Junctions - microbiology; HeLa Cells; Humans; Immunity, Innate; Interleukin-8 - analysis; Interleukin-8 - immunology; Life Sciences; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeriosis - enzymology; Listeriosis - immunology; MAP Kinase Signaling System - immunology; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - immunology; NF-kappa B - metabolism; Peptidoglycan - immunology; Salmonella typhimurium; Shigella flexneri; Shigella flexneri - enzymology; Shigella flexneri - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2010.10.015

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. [Display omitted] ► Inflammatory signals propagate from infected to uninfected bystander cells ► NF-κB and MAP kinases are activated in uninfected bystander cells ► Uninfected bystander cells produce IL-8 during bacterial infection ► The propagation of proinflammatory signals is mediated through gap junctions