Figure 2: Functional validation of CD58 in antifungal host denfense.

(a) Common phenotype enrichment in the mouse using the Mouse Genome Informatics (MGI) phenotype data of the 93 genes differentially expressed at 24 h between control and CD58 siRNA cells. (b) CD58 gene expression levels in wild-type macrophages at 0, 6 and 24 h upon Candida infection were extracted from the microarray experiment. (c) Human monocyte-derived macrophages were transfected with control and CD58 siRNA, respectively, for 48 h. Macrophages were co-incubated with live C. albicans for an additional 24 h. Representative microscopic photos of the Candida outgrowth through the macrophage are shown. The magnification is × 40. (d) First panel: macrophages were transfected with control and TAGAP siRNA, respectively, for 48 h. Macrophages were co-incubated with live C. albicans for an additional 24 h. Second panel: control and CD58 siRNA-transfected macrophages were co-incubated with live C. albicans Δhgc1strain for an additional 24 h. Representative microscopic photos of the Candida outgrowth through the macrophage are shown. (e) Human monocyte-derived macrophages from 66 healthy volunteers with different CD58 SNP rs12025416 genotypes were stimulated with Candida for 24 h (grey bars) or with LPS for 24 h (blue bars), and the supernatant was collected for IL-6 and TNF-α measurements. Average values of Candida-induced IL-6 levels among CT individuals is 62.68 and among TT is 218.19; whereas for LPS it is 592.71 in CT group and 650.26 in TT group. Average values of Candida-induced TNF-α levels among CT individuals is 603.57 and among TT is 1,122.88; whereas for LPS it is 570.02 in CT group and 648.36 in TT group. The error bars indicate s.e.m.. The correlation between cytokine production and genotypes was tested by the Wilcoxon rank sum test. NS; not significant.