Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. Electronic address: Alireza_trtr@yahoo.com.
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Loghmani
Department of Infectious Diseases, University of Jahrom Medical Science, Jahrom, Iran.
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Raoofi
Department of Infectious Diseases, University of Jahrom Medical Science, Jahrom, Iran.
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Ownagh
Department of Infectious Diseases, University of Jahrom Medical Science, Jahrom, Iran.
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Delirezh
D000528:Alternaria / Q000276:immunology*; D060487:Alternariosis / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines
Alternaria alternata; Dendritic cell; Environmental fungus; Th2/Th17