Data from: Impaired T Cell Responsiveness to Interleukin-6 in Hematological Patients with Invasive Aspergillosis

Invasive mold infections (IMI) are among the most devastating
complications following chemotherapy and hematopoietic stem cell
transplantation (HSCT), with high mortality rates. Yet, the molecular
basis for human susceptibility to invasive aspergillosis (IA) and
mucormycosis remain poorly understood. Herein, we aimed to characterize
the immune profile of individuals with hematological malignancies (n = 18)
who developed IMI during the course of chemotherapy or HSCT, and compared
it to that of hematological patients who had no evidence of invasive
fungal infection (n = 16). First, we measured the expression of the
pattern recognition receptors pentraxin 3, dectin-1, and Toll-like
receptors (TLR) 2 and 4 in peripheral blood of chemotherapy and HSCT
recipients with IMI. Compared to hematological controls, individuals with
IA and mucormycosis had defective expression of dectin-1; in addition,
patients with mucormycosis had decreased TLR2 and increased TLR4
expression. Since fungal recognition via dectin-1 favors T helper 17
responses and the latter are highly dependent on activation of the signal
transducer and activator of transcription (STAT) 3, we next used
phospho-flow cytometry to measure the phosphorylation of the transcription
factors STAT1 and STAT3 in response to interferon-gamma (IFN-γ) and
interleukin (IL)-6, respectively. While IFN-γ/STAT1 signaling was similar
between groups, naïve T cells from patients with IA, but not those with
mucormycosis, exhibited reduced responsiveness to IL-6 as measured by
STAT3 phosphorylation. Furthermore, IL-6 increased Aspergillus-induced
IL-17 production in culture supernatants from healthy and hematological
controls but not in patients with IA. Altogether, these observations
suggest an important role for dectin-1 and the IL-6/STAT3 pathway in
protective immunity against Aspergillus.