Figure 7. Sustained NLRC4 activation causes tissue damage.

WT or Ncf1^−/−mice were infected with ST-WT or ST-FliC^ON for 48 h. WT mice were infected with 10⁵ CFU of each strain. Ncf^−/− mice infected with 10³ or 10⁴ CFU ST-WT, or 10³ CFU ST-FliC^ON; note that bacterial loads 48h post infection were similar between mice infected with 10⁴ CFU ST-WT and 10³ CFU ST-FliC^ON (see f). (a–d) Histopathology of spleens from WT or Ncf1^−/−mice infected with ST-WT or ST-FliC^ON. WT mice infected wit ST-WT (a) had multifocal neutrophilic to necrosuppurative splenitis and red pulp congestion. In contrast, WT mice infected with ST-FliC^ON (b) had nearly normal splenic morphology. Splenic lesions in the Ncf1^−/−mice infected with 10³ ST-FliC^ON (d) were severe and consisted of marked red and white pulp necrosis. Less severe changes were seen in Ncf1^−/−mice infected with 10⁴ ST-WT (c), including red pulp congestion, thrombosis, neutrophilic to necrosuppurative splenitis, while the white pulp was relatively spared. Scale bar = 100μm. (e) Scoring of pathologic changes in spleens from Ncf1^−/−mice (n=3 per inoculum). (f) CFU from the spleen were determined (n=3 per inoculum). Two doses of ST-WT were used in Ncf1^−/−mice in order to compare to ST-FliC^ON infected mice normalized for either initial dose or 48h bacterial load; Ncf1^−/−infected with 10⁴ CFU ST-WT have similar bacterial loads to Ncf1^−/−mice infected with 10³ ST-FliC^ON. * = p < 0.05, NS = p > 0.05.