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

ABSTRACT

Background: 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.

KEYWORDS:

• Invasion fungal infections
• Th17 cells
• allogeneic hematopoietic stem cell transplantation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by National Natural Science Foundation of China: [Grant Number No. 81501422]; Qingdao Outstanding Health Professional Development Fund: [Grant Number 2016]; Shandong Provincial Medicine and Health Science Technology Development Planning: [Grant Number 2015WSA02040].