Oral Exposure to House Dust Mite Activates Intestinal Innate Immunity

Scope: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. Methods and results: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Conclusion: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.

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Abstract 1772: Cardiomyocyte Damage-Released S100A1 Protein Evokes A Proinflammatory Phenotype In Cardiac Fibroblasts

Circulation ◽

10.1161/circ.118.suppl_18.s_386-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

David Rohde ◽

Melanie Boerries ◽

Herzog Nicole ◽

Gang Qiu ◽

Philipp Ehlermann ◽

...

Keyword(s):

Western Blotting ◽

Immune Cells ◽

Nuclear Translocation ◽

Cardiac Fibroblasts ◽

Innate Immune ◽

Host Cells ◽

Boyden Chamber ◽

Innate Immune Cells ◽

Danger Signal

Background: S100A1, a cardiomyocyte specific inotropic calcium sensor protein, is released from infarcted human myocardium in the extracellular environment and circulation, reaching peak serum levels (1–2 μM) 8–9 hours after clinical onset. As growing evidence indicates that S100 proteins can act as pre-existing danger signals triggering the innate immune system into action upon release from injured host cells, we hypothesized that damage-released S100A1 can act as a cardiac danger signal alerting innate immune cells. Methods and Results: Here we report for the first time that necrotic cardiomyocytes release S100A1 protein in vitro, which is exclusively internalized by cardiac fibroblasts (CFs) in a clathrin- and caveolin-independent manner as shown by IF. Internalized S100A1 specifically activated MAPKs/SAPKs (p38, ERK1/2 and JNK) resulting in nuclear translocation of p65 (NF-kB) as assessed by Western blotting, EMSA and IF. In turn, S100A1 triggered an inflammatory gene program in CFs including enhanced expression of adhesion molecules, integrins, chemokines and cytokines including I-CAM, V-CAM, CD11b/18, IL1-alpha, MCP-1, TNF-alpha, SDF-1 among others as obtained by RT-PCR, Western blotting and ELISA. This resulted in enhanced chemoattraction and adhesion of monocytotic and stem cells to S100A1-activated CF as shown by Boyden-chamber and adhesion assays. In line with their proinflammatory transition, S100A1-activated CFs exhibited decreased collagen-1/-3 expression and de-novo collagen production, enhanced collagenolytic MMP-9 abundance and activity and increased levels of the antiangiogenic matricellular factor thrombospondin-2 reflecting extracellular matrix net degradation. Importantly, the immun-modulatory and antifibrotic actions of S100A1 protein in vitro were restricted to CFs, RAGE independent and occurred at concentrations (0.1–1 μM) that were found in patients after AMI. Conclusion: Our in vitro results indicate that S100A1 has the properties of a pre-exisiting endogenous cardiomyocyte danger signal transforming cardiac fibroblasts into immunmodulatory cells that might recruit innate immune cells to the site of cardiac injury and link cardiomyocyte damage to post-MI inflammation.

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Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages

The Journal of Immunology ◽

10.4049/jimmunol.1901348 ◽

2021 ◽

pp. ji1901348

Author(s):

Kathrin Thiem ◽

Samuel T. Keating ◽

Mihai G. Netea ◽

Niels P. Riksen ◽

Cees J. Tack ◽

...

Keyword(s):

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Human Monocytes ◽

Murine Macrophages ◽

Proinflammatory Responses

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Diagnostic significance of in vitro T-cell proliferative responses to house-dust mite Der p 1 in children with dust-mite allerev

Allergy ◽

10.1111/j.1398-9995.1996.tb04476.x ◽

1996 ◽

Vol 51 (11) ◽

pp. 842-846

Author(s):

G. Horneff ◽

C. Schou ◽

V. Wahn

Keyword(s):

T Cell ◽

House Dust ◽

House Dust Mite ◽

Diagnostic Significance ◽

Dust Mite ◽

Der P 1

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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

Journal of Biomedical Science ◽

10.1186/s12929-019-0598-6 ◽

2019 ◽

Vol 26 (1) ◽

Cited By ~ 1

Author(s):

Ming-Han Chen ◽

Ming-Ting Huang ◽

Wen-Kuang Yu ◽

Shinn-Shing Lee ◽

Jia-Horng Wang ◽

...

Keyword(s):

House Dust ◽

House Dust Mite ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Specific Binding ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Dust Mite ◽

Der P 2

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.

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