10.5061/DRYAD.N9B7R
Camargo, Jose F.
University Health Network
University of Toronto
Bhimji, Alyajahan
University Health Network
University of Toronto
Kumar, Deepali
University Health Network
University of Toronto
Kaul, Rupert
University Health Network
University of Toronto
Pavan, Rhea
University Health Network
University of Toronto
Schuh, Andre
University Health Network
Seftel, Matthew
University Health Network
Lipton, Jeffrey H.
University Health Network
Gupta, Vikas
University Health Network
Humar, Atul
University Health Network
University of Toronto
Husain, Shahid
University Health Network
University of Toronto
Data from: Impaired T Cell Responsiveness to Interleukin-6 in
Hematological Patients with Invasive Aspergillosis
Dryad
dataset
2016
peripheral blood mononuclear cells
Toll-like receptors
invasive mold infections
mucormycosis
interleukin (IL)-6
Aspergillus
invasive aspergillosis
T helper 17
dectin-1
pentraxin 3
phospho-flow
patter recognition receptors
Hematopoietic stem cell transplantation
signal transducer and activator of transcription (STAT)
interferon-gamma
2016-03-31T00:00:00Z
2016-03-31T00:00:00Z
en
https://doi.org/10.1371/journal.pone.0123171
269653 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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.
Flow Results CompiledCompilation of raw data from all flow cytometry
experiments including surface staining and phosphoflow. Sheet 1 is all the
data for each patient, Sheet 2 is the log2 fold change of the MFI used for
the heat map (figure 2), Sheet 3 compares samples collected <30d
after diagnosis vs >30d after diagnosis, Sheet 4 examines the
effect of freeze-thawing samples on surface staining. Statistical analysis
on each sheet.ELISA Data (PTX3 IL17 and IFN)Data from PTX3, IL-17 and
IFN-gamma ELISAs.