Decreased levels of Th17 cells are associated with invasion fungal infections after allogeneic hematopoietic stem cell transplantation

Abstract

ABSTRACTBackground: Delayed immune reconstitution is an important risk factor for increased susceptibility to fungal pathogens. However, little is known about the association between the recovery of CD4+T cell subsets and invasion fungal infections (IFIs) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to analyze the immune reconstitution characteristics of CD4+T cell subsets and their association with the incidence of IFIs over the first 3 months after allo-HSCT.Methods: Fifty-three patients were included, 13 with IFIs. We assessed CD4+T cell subsets and the mRNA expression of specific transcription factors T-bet, GATA3, RORγt, and Foxp3 in peripheral blood mononuclear cells over three time points. The serum levels of IFN-γ, IL-6, IL-10, and TGF-β were detected using the enzyme-linked immunosorbent assay.Results: CD4+T cell subsets increased progressively in non-IFI patients after allo-HSCT. In IFI patients, Th17 cell counts were significantly decreased compared to non-IFI patients at 3 months after allo-HSCT. IFI patients showed the lower ratios of RORγt/GATA3 and RORγt/Foxp3 compared with non-IFI patients. In addition, we observed increased levels of IFN-γ and IL-10 in IFI patients after allo-HSCT. In the multivariate analysis, the occurrence of IFIs was independently associated with the incidence of IFIs. Finally, we observed a lower CD4:CD8 ratio in IFI patients and its association with Th17 cells.Conclusions: These findings supported that Th17 cells may be involved in the immune pathology of IFIs after allo-HSCT.