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. 2016 Jul 1;7:12077. doi: 10.1038/ncomms12077

Figure 10. Proposed two-stage model illustrating the two sequential waves of eicosanoids produced in response to S. Typhimurium infection.

Figure 10

Stage 1, step1: infected cells release Cxcl8 and LTB4 in an inflammasome-independent manner. Stage 1, step 2: neutrophils are recruited to the infection sites via Cxcl8 and LTB4 gradients and phagocytose ST. Stage 2, step1: ST taken up by neutrophils localized to the Salmonella-containing vacuole (SCV) where it uses its T3SS to translocate bacterial proteins to the cytosol. Flagellin, being one of those bacterial proteins, can be recognized by cytosolic NLRs, probably NLRP3 and NLRC4, which consequently induce the assembly of a Gbp4 and Asc through CARD domains allowing the subsequent recruitment of pro-Caspa. Stage 2, step2: the hydrolysis of GTP to GDP or GMP by Gbp4 results in a conformational change in the inflammasome complex that allows the activation of Caspa via autocleavage, resulting in the induction of PG biosynthesis through the activation of cPla2 and via Ptgs (also known as cyclooxygenases).