Ragweed subpollen particles of respirable size activate human dendritic cells

• Published in: PloS one 2012-12, Vol.7 (12), p.e52085-e52085
• Main Authors: Pazmandi, Kitti, Kumar, Brahma V, Szabo, Krisztina, Boldogh, Istvan, Szoor, Arpad, Vereb, Gyorgy, Veres, Agota, Lanyi, Arpad, Rajnavolgyi, Eva, Bacsi, Attila
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Allergens; Allergens - immunology; Allergies; Ambrosia - immunology; Ambrosia artemisiifolia; Antigens; Antigens, CD - immunology; Antigens, CD - metabolism; Asthma; Biology; Biophysics; Blood & organ donations; Blood transfusions; CD3 antigen; CD40 antigen; CD80 antigen; CD86 antigen; Cell activation; Cell culture; Cell Proliferation; Cell surface; Chemistry; Coculture Techniques; Confocal; Deactivation; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Heat treatment; Histocompatibility antigen HLA; HLA antigens; HLA-DQ Antigens - immunology; HLA-DQ Antigens - metabolism; Humans; Immune response; Immunology; Inactivation; Inflammation; Interferon; Interleukin 10; Interleukin 17; Interleukin 4; Interleukin 6; Interleukin 8; Interleukins - immunology; Interleukins - metabolism; Intracellular levels; Lungs; Lymphocytes; Lymphocytes T; Medicine; Microscopy; Monocytes; NAD(P)H oxidase; NADP - immunology; NADP - metabolism; NADPH Oxidases - immunology; NADPH Oxidases - metabolism; Oxidase; Oxidases; Oxidative stress; Oxygen; Particle size; Particulates; Phagocytosis; Phagocytosis - immunology; Pollen; Pollen - immunology; Pretreatment; Proteins; Reactive oxygen species; Reactive Oxygen Species - immunology; Reactive Oxygen Species - metabolism; Respiratory System - immunology; Respiratory System - metabolism; Respiratory tract; Scanning microscopy; Science; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - immunology; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052085

Ragweed (Ambrosia artemisiifolia) pollen grains, which are generally considered too large to reach the lower respiratory tract, release subpollen particles (SPPs) of respirable size upon hydration. These SPPs contain allergenic proteins and functional NAD(P)H oxidases. In this study, we examined whether exposure to SPPs initiates the activation of human monocyte-derived dendritic cells (moDCs). We found that treatment with freshly isolated ragweed SPPs increased the intracellular levels of reactive oxygen species (ROS) in moDCs. Phagocytosis of SPPs by moDCs, as demonstrated by confocal laser-scanning microscopy, led to an up-regulation of the cell surface expression of CD40, CD80, CD86, and HLA-DQ and an increase in the production of IL-6, TNF-α, IL-8, and IL-10. Furthermore, SPP-treated moDCs had an increased capacity to stimulate the proliferation of naïve T cells. Co-culture of SPP-treated moDCs with allogeneic CD3(+) pan-T cells resulted in increased secretion of IFN-γ and IL-17 by T cells of both allergic and non-allergic subjects, but induced the production of IL-4 exclusively from the T cells of allergic individuals. Addition of exogenous NADPH further increased, while heat-inactivation or pre-treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, strongly diminished, the ability of SPPs to induce phenotypic and functional changes in moDCs, indicating that these processes were mediated, at least partly, by the intrinsic NAD(P)H oxidase activity of SPPs. Collectively, our data suggest that inhaled ragweed SPPs are fully capable of activating dendritic cells (DCs) in the airways and SPPs' NAD(P)H oxidase activity is involved in initiation of adaptive immune responses against innocuous pollen proteins.