Transcription factors of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) family control important signaling pathways in the regulation of the host innate immune system. Various bacterial pathogens in the human gastrointestinal tract induce NF-ĸB activity and provoke pro-inflammatory signaling events in infected epithelial cells. NF-ĸB activation requires the phosphorylation-dependent proteolysis of inhibitor of ĸB (IĸB) molecules including the NF-ĸB precursors through
ubiquitin-mediated proteolysis. The canonical NF-ĸB pathway merges on IĸB
kinases (IKKs), which are required for signal transduction. Using CRISPR-Cas9 technology, secreted embryonic
alkaline phosphatase (SEAP) reporter assays and
cytokine enzyme-linked
immunosorbent assay (ELISA), we demonstrate that the
actin-binding protein cortactin is involved in NF-ĸB activation and subsequent
interleukin-8 (IL-8) production upon
infection by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa. Our data indicate that
cortactin is needed to efficiently activate the c-
Sarcoma (
Src) kinase, which can positively stimulate NF-ĸB during
infection. In contrast,
cortactin is not involved in activation of NF-ĸB and
IL-8 expression upon
infection with Campylobacter species C. jejuni, C. coli or C. consisus, suggesting that Campylobacter species pluralis (spp.) induce a different signaling pathway upstream of
cortactin to trigger the innate immune response.