Fig. 7: NLRP3 inflammasome inhibitors protect against Aspergillus-induced EoE in a mouse experimental model.

A representative photomicrograph of immunofluorescence analysis of NLRP3 and IL-18 double-positive cells in esophageal tissue sections of mice challenged with saline and A. fumigatus challenged (a, i, iv). A decreased level of NLRP3 and IL-18 double-positive cells in mice A. fumigatus-challenged mice treated with MCC950 (a, ii, v) BHB (a, iii, vi) and the morphometric quantitation showed statistically significant decreased levels of NLRP3+IL-18+ cells by antagonist of NLRP3 treatment (b). The immunofluorescence photomicrograph showed a similar decrease of NLRP3+IL-18+ cells by caspase1 inhibitor VX-765 compared to controls (c, i–ii, d, i–ii). Morphometric analyses show a statistically significant decrease in NLRP3+IL-18+ cells in A. fumigatus-challenged mice compared to A. fumigatus-challenged mice treated with the inhibitor of caspase1 (e). A representative photomicrograph of Anti-MBP+ eosinophils from esophageal sections of mice challenged with saline (f, i) MCC950 (f, ii), BHB (f, iii), and VX-765 (f, iv) and Aspergillus challenged (f, v) A. fumigatus + MCC950 (f, vi), A. fumigatus + BHB (f, vii), and A. fumigatus + VX-765 (f, viii) are shown. Morphometric analyses show a significant decrease in anti-MBP+ eosinophils in A. fumigatus-challenged mice compared to those treated with NLRP3 inhibitors, MCC950, BHB, and VX-765 (g). A representative photomicrograph of MBP+ eosinophil levels in mice challenged with saline corn extract and MCC950 treated corn challenged mice (h, i–iii) with morphometric quantitation analysis (i). IL-18 estimation by ELISA in esophageal tissue samples, expressed as pg/mg of tissue (j). Western blot analysis of NLRP3-IL-18-caspase-1, IL-18, EPX and TGFβ (k) are presented. Data are expressed as mean ± SD, n = 6–8 mice/group. *p < 0.05; **p < 0.001; ***p < 0.001; ****p < 0.0001. All photomicrographs shown are in original magnification of ×400 (scale bar 20 µm). EP epithelium, LP lamina propria, MS muscular mucosa, LU lumen.