Fig. 4: CT135 activates the NLRP3 inflammasome through the TLR2/MyD88 signaling pathway.
a Secretion of IL-6 in CtD and CtD CT135- infected BMDN derived from C57BL/6, TLR2−/−, MyD88−/− mice (n = 3 mice per group). b Secretion of IL-1β in CtD and CtD CT135-infected BMDN derived from C57BL/6, TLR2−/−, MyD88−/− mice (n = 3 mice per group). c Secretion of IL-1β in CtD and CtD CT135− infected BMDN derived from C57BL/6, NLRP3−/−, Caspase1−/− mice (n = 3 mice per group). (a–c two-tailed unpaired student’s t tests). a–c Result shown are representatives of two independent experiments. d CtD infections of TLR2−/−, MyD88−/−, NLRP3−/−, Caspase1−/− mice were significantly higher at day 7 pi. (n = 10 mice, pooled from two independent experiments, two-tailed Mann–Whitney test). e Quantification of gross uterine horn pathology of CtD infected C57BL/6, TLR2−/−, MyD88−/−, NLRP3 −/−, Caspase1−/− infected mice at day 56 pi (n = 10 mice per group, pooled from two independent experiments, two-tailed Mann–Whitney test). f A model of CT135 dependent neutrophil killing through NLRP3 inflammasome via TLR2/MyD88 signaling. Signal one is triggered by an abortive CtD infection in phagocytes resulting EB to RB transition with an accompanying degradation of chlamydial OM lipoprotein(s)42. We hypothesize CT135 exports degraded OM lipoprotein engaging inclusion membrane TLR243. This process results in signaling by MyD88 and NF-κB to upregulate NLRP3 and pro-IL-1β expression. Signal 2 activation of NLRP3 is the result of infection-induced cellular stress34. This CtD phagocyte interaction activates the NLRP3 inflammasome resulting in phagocytic cell death and IL-1β secretion. a–e Data are shown as the mean ± SD.
