FIG 2.
SpeB and caspase-1 contribute to IL-1β generation in the nasopharynx. Effects of IL-1 and inflammasome signaling on GAS survival. (A) C57BL/6, casp-1/11−/−, or IL1R1−/− mice were inoculated intranasally with 108 CFU of wild-type GAS M1T1 5448. Mice were euthanized after 24 h, nasopharyngeal lavage fluids were plated to enumerate CFU, and cytokine levels were quantified by ELISA and IL-1R reporter assay. (B and C) Role of SpeB and CovRS in GAS survival. C57BL/6 mice were given anakinra (50 μg/kg) or PBS and infected as described above with wild-type, ΔspeB, or AP covS-frameshift GAS, and CFU and cytokines were examined as described above. (D) Role of host pathways in selection for covS-frameshift SpeB− clones. Isolated colonies from the experiments for panels A, B, and C were screened for SpeB hydrolysis of azocasein, and the fraction where SpeB activity is lost is indicated. ND, none detected (for experiments where no GAS was recoverable from the mouse). Data are means ± SD (n = 5 each) and are representative of at least 3 experiments. *, P < 0.05; **, P < 0.005; ***, P < 0.0005; ns, not significant.