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Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4

Figure 7

Live S. pneumoniae promotes IL-1β secretion by DC in a NLRP3-dependent manner and this requires PLY.

DC (6.25×105/ml) from C57BL/6 or NLRP3−/− mice were incubated for 24 hours with medium alone, with wild-type S. pneumoniae (D39; 10 bacteria:1DC) or with PLY-deficient bacteria (PLN; 10 bacteria:1 DC). As a positive control for IL-1β secretion and NLRP3 inflammasome activation, DC were primed with LPS (100 ng/ml) for 23 hours prior to one hour stimulation with ATP (2.7 mg/ml). Following incubation, supernatants were removed and assayed for IL-1β, IL-1α, TNF-α and IL-6. Results are mean cytokine concentrations (+ SEM) for triplicate samples. *** P<0.001, NLRP3−/− vs. C57BL/6 DC stimulated with the same treatments, ### P<0.001, D39 vs. PLN bacteria in C57BL/6 DC, ••• P<0.001, D39 vs. PLN bacteria in NLRP3−/− DC.

Figure 7

doi: https://doi.org/10.1371/journal.ppat.1001191.g007