In vitro immune responses of human PBMCs against Candida albicans reveals fungal and leucocyte phenotypes associated with fungal persistence

Abstract

AbstractAlthough there is a growing understanding of immunity against Candida albicans, efforts need to be pursued in order to decipher the cellular mechanisms leading to an uncontrolled immune response that eventually oppose disease eradication. We describe here significant intra- and inter-subject variations in immune response patterns of major human leucocyte subsets following an in vitro challenge with C. albicans clinical isolates. We also observed that there are Candida isolate-dependent changes in leucocyte phenotypes. Through a combination of multiple fungal growth and flow cytometric measurements, coupled to the tSNE algorithm, we showed that significant proliferation differences exist among C. albicans isolates, leading to the calculation of a strain specific persistent index. Despite substantial inter-subject differences in T cells and stability of myeloid cells at baseline, our experimental approach highlights substantial immune cell composition changes and cytokine secretion profiles after C. albicans challenge. The significant secretion of IL-17 by CD66+ cells, IFN-γ and IL-10 by CD4+ T cells 2 days after C. albicans challenge was associated with fungal control. Fungal persistence was associated with delayed secretion of IFN-γ, IL-17, IL-4, TNF-α and IL-10 by myeloid cells and IL-4 and TNF-α secretion by CD4+ and CD8+ T cells. Overall, this experimental and analytical approach is available for the monitoring of such fungal and human immune responses.