scholarly journals Antibody blockade of Dectin-2 suppresses house dust mite-induced Th2 cytokine production in dendritic cell- and monocyte-depleted peripheral blood mononuclear cell co-cultures from asthma patients

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Ming-Han Chen ◽  
Ming-Ting Huang ◽  
Wen-Kuang Yu ◽  
Shinn-Shing Lee ◽  
Jia-Horng Wang ◽  
...  

Abstract Background Dectin-2, which is a C-type lectin, interacts with the house dust mite (HDM) Dermatophagoides pteronyssinus allergen. This study aimed to investigate whether Dectin-2 blockade by antagonistic monoclonal antibodies (MoAbs) attenuates HDM-induced allergic responses. Methods Two anti-Dectin-2 MoAbs were generated and validated for specific binding to Dectin-2 Fc fusion protein (Dectin-2.Fc) and inhibition of Dectin-2.Fc/HDM interaction. Patients with asthma exhibiting high titers of anti-D. pteronyssinus IgE were enrolled. Peripheral blood mononuclear cells with depleted CD14+ monocytes were obtained from these patients and co-cultured with autologous monocyte-derived conventional dendritic cells in the presence of D. pteronyssinus or its group 2 allergens (Der p 2). Interleukin (IL)-5 and IL-13 levels in the culture supernatants were determined using ELISA in the presence or absence of anti-Dectin-2 MoAbs. Results Two MoAbs, 6A4G7 and 17A1D10, showed specific binding to recombinant Dectin-2.Fc and inhibited HDM binding to Dectin-2.Fc. Both anti-Dectin-2 MoAbs inhibited IL-5 and IL-13 production in co-cultures with Der p 2 stimulation in a dose-dependent manner. 6A4G7 and 17A1D10 (3 μg/mL) significantly inhibited Der p 2-induced (3 μg/mL) IL-5 production by 69.7 and 86.4% and IL-13 production by 84.0 and 81.4%, respectively. Moreover, this inhibitory effect of the two MoAbs remained significant in the presence of D. pteronyssinus. Conclusions Anti-Dectin-2 MoAbs significantly inhibited HDM-induced allergic responses in vitro and therefore have the potential to become therapeutic agents in mite-induced allergic diseases.

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Lu Yan-ming ◽  
Cao Lan-fang ◽  
Li Chen ◽  
Li Ya-qin ◽  
Chen Wei ◽  
...  

To investigate the effects of specific immunotherapy on the NKT cells in peripheral blood and the ability of NKT cells to proliferate in response to alpha-galactosylceramide (alpha-GalCer) in house-dust-mite- (HDM-) sensitized asthma children, peripheral blood mononuclear cells were isolated from 42 asthmatic children, of whom 24 were on specific immunotherapy (SIT) for more than a year and 20 were healthy. Compared with control group, the ratio of peripheral blood NKT and CD4+NKT cells was significantly decreased (P<0.01) and was elevated in SIT asthma group (P<0.05), respectively, but it was still less than the normal control group (P<0.01). The level of IL-4 in serum secreted by NKT cells in asthma group was significantly higher than that of control group (P<0.01), particularly apparent after 72 hours. The level of IL-4 in SIT group decreased significantly (P<0.01). The level of IL-10 in serum secreted by NKT cells in asthma group was decreased significantly than that of the control group (P<0.01) especially in 48 hours, while that of SIT group was increased significantly (P<0.01). These results suggest that the pathogenesis of asthma may be related to the ratio and dysfunction of NKT and CD4+NKT cells.


Cytokine ◽  
2016 ◽  
Vol 88 ◽  
pp. 184-192 ◽  
Author(s):  
Hélio Galdino ◽  
Rodrigo Saar Gomes ◽  
Jessica Cristina dos Santos ◽  
Lívia Lara Pessoni ◽  
Anetícia Eduarda Maldaner ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Maryse Thivierge ◽  
Sylvie Turcotte ◽  
Marek Rola-Pleszczynski ◽  
Jana Stankova

In order to determine the potential for allergen to modulate T cell expression of the CysLT1receptor and responsiveness to leukotrienes, peripheral blood mononuclear cells from house dust mite-allergic or nonallergic individuals were incubated withD. pteronyssinusallergen (Der p). Baseline CysLT1expression was similar in both groups of donors, but Der p significantly enhanced CysLT1expression in CD4+and CD8+T cells of only allergic individuals and induced enhanced responsiveness of CD4+T cells to LTD4in terms of calcium mobilisation. This effect was prevented by the CysLT1antagonist MK571. Der p also induced IL-4 and IL-10 production, and neutralizing antibody to IL-4 prevented both the enhanced CysLT1expression and the enhanced responsiveness of T cells to LTD4induced by Der p. In allergic individuals, Der p also induced T cell proliferation and a Th2-biased phenotype. Our data suggest that, in allergen-sensitized individuals, exposure to allergen can enhance T cell expression of CysLT1receptors through a mechanism involving IL-4 production. This, in turn, would induce CD4+T cell responsiveness to cysteinyl-leukotrienes and Th2 cell activation.


Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 109
Author(s):  
Muhammad Ehsan ◽  
Muhammad Haseeb ◽  
Ruisi Hu ◽  
Haider Ali ◽  
Muhammad Ali Memon ◽  
...  

During host-parasite interactions, binding of excretory/secretory proteins (ESPs) on the host immune cells is considered the fundamental phase for regulation of immune responses. In this study, gene encoding Haemonchus contortus tropomyosin (Hc-TpMy), was successfully cloned and expressed, and the recombinant protein after host cell surface attachment was evaluated for immune functional analysis with goat peripheral blood mononuclear cells (PBMCs) in vitro. The isopropyl-β-D-thiogalactopyranoside (IPTG)-induced recombinant protein was successfully recognized by the sera of rat experimentally infected with rHc-TpMy. The immunofluorescence assay detected attachment of rHc-TpMy on the surface of host PBMCs. Furthermore, immunoregulatory roles of rHc-TpMy on cytokines expression, PBMC proliferation, migration, nitric oxide (NO) production, apoptosis and monocytes phagocytosis were observed. The results showed that expression of IL-4 and IFN-γ cytokines, cell proliferation, NO production and PBMC migration were significantly suppressed by goat PBMCs after co-incubation with rHc-TpMy protein. However, the productions of IL-10, IL-17 and TGF-β1 cytokines, PBMCs apoptosis and monocytes phagocytosis were elevated at dose dependent manner. Our findings indicated that rHc-TpMy is an important ES binding protein exhibit distinct immuno-suppressive roles on goat PBMCs which might be a potential molecular target to control haemonchosis in future.


2021 ◽  
Vol 2 ◽  
Author(s):  
Kazuhiro Ogi ◽  
Mahnaz Ramezanpour ◽  
Sha Liu ◽  
Jannatul Ferdoush Tuli ◽  
Catherine Bennett ◽  
...  

Background:Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). However, the effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear.Methods: Air–liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects (non-AR) (n = 9) and HDM-AR patients (n = 9) were treated with Der P 1 and Der P 2, followed by testing the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextrans and immunofluorescence of claudin-1 and ZO-1. Interleukin-6 (IL-6) production was evaluated by ELISA.Results: Der p 1 reduced TEER significantly in a transient and dose-dependent manner in HNEC-ALI cultures from HDM-AR and non-AR patients, whilst the paracellular permeability was not affected. TEER was significantly reduced by Der p 1 at the 10-min time point in HDM-AR patients compared to non-AR patients (p = 0.0259). Compared to no-treatment control, in HNECs derived from HDM-AR patients, Der p 1 significantly cleaved claudin-1 after 30 min exposure (72.7 ± 9.5 % in non-AR group, 39.9 ± 7.1 % in HDM-AR group, p = 0.0286) and induced IL-6 secretion (p = 0.0271).Conclusions: Our results suggest that patients with HDM-AR are more sensitive to Der p 1 than non-AR patients with increased effects of Der p1 on the mucosal barrier and induction of inflammation, indicating an important role for Der p1 in sensitization and HDM-AR development.


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