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Vol. 45. Issue 2.
Pages 175-182 (March - April 2017)
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Vol. 45. Issue 2.
Pages 175-182 (March - April 2017)
Original Article
DOI: 10.1016/j.aller.2016.07.005
Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation
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A. Loghmania,
Corresponding author
Alireza_trtr@yahoo.com

Corresponding author.
, R. Raoofib, A. Ownaghb, N. Delirezhb
a Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
b Department of Infectious Diseases, University of Jahrom Medical Science, Jahrom, Iran
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Abstract
Introduction

Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure.

Materials and methods

Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups.

Results

The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group.

Conclusion

The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.

Keywords:
Alternaria alternata
Dendritic cell
Environmental fungus
Th2/Th17
Abbreviations:
A. alternata
CD
DCs
FACS
FBS
GM-CSF
HLA-DR
IFN-γ
IL
ImDC
MCM
mDC
MFI
MoDc
PBMC
Th
Treg

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