TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway

Moisan, Jacques; Camateros, Pierre; Thuraisingam, Thusanth; Marion, Dominique; Koohsari, Hossein; Martin, Pauline L.; Boghdady, Marie-Linda; Ding, Aihao; Gaestel, Matthias; Guiot, Marie‐Christine; Martin, James G.; Radzioch, Danuta

doi:10.1152/ajplung.00440.2005

Cited by 85 publications

(73 citation statements)

References 41 publications

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“…Systemic application of R848 or poly(I:C) during allergen sensitization results in reduction of allergic airway disease after allergen challenge (36). In addition, systemic treatment of sensitized animals during primary challenge (37) or during secondary Ag challenge (36) again reduced allergic airway disease. Application of TLR ligands into the lung prior to airway challenge efficiently prevents induction of allergic diseases probably by a mechanism depending on CD8 + T cells (38).…”

Section: Discussionmentioning

confidence: 99%

“…For intracellular cytokine analysis, we used allophycocyanin-labeled IFN-g (BD Pharmingen), PE-labeled IL-17A (BD Pharmingen), and PE-labeled IL-5 (BD Pharmingen). Abs were incubated at 4˚C for [30][31][32][33][34][35][36][37][38][39][40] ), single-cell suspensions of tracheal lymph nodes or lung cells were adjusted and surface stained for PeCy7-labeled CD4 PeCy7 and PE-labeled CD25 (all BD Pharmingen) as described. Foxp3 staining was performed following the advice of the manufacturer of the fixation/permeabilization set (eBioscience).…”

Section: Assessment Of Intracellular Cytokine Staining and Regulatorymentioning

confidence: 99%

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TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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Epidemiological studies suggest that viral infections during childhood are a risk factor for the development of asthma. However, the role of virus-specific pattern recognition receptors in this process is not well defined. In the current study, we compare the effects of the inhaled viral TLR ligands polyinosinic-polycytidylic acid (TLR3) and resiquimod (TLR7/8) on sensitization to a model allergen (OVA) in a murine model. Both compounds enhance the migration, activation, and Ag-processing of myeloid dendritic cells from the lung to the draining lymph nodes comparable to the effects of LPS. Application of polyinosinic-polycytidylic acid [poly(I:C)] or LPS induces production of allergen-specific IgE and IgG1, whereas resiquimod (R848) had no effect. In addition, rechallenge of mice with OVA resulted in airway inflammation and mucus production in animals that received either poly(I:C) or LPS but not after application of R848. In summary, these results show that activation of TLR3 in combination with inhaled allergen results in induction of dendritic cell activation and migration similar to the effects of LPS. This leads to the development of allergic airway disease after allergen rechallenge, whereas mice treated with R848 did not develop allergic airway disease. These findings give further insight into the effects of stimulation of different TLRs on the development of asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Intracellular Cytokine Staining and Regulatorymentioning

confidence: 99%

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Reuter¹,

Dehzad²,

Martin³

et al. 2012

The Journal of Immunology

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“…And, it is even more interesting when considering that protection from anaphylactic death is not usually described in the literature [41][42][43][44]. Therefore, this effect is a significant finding for its application in immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis

Gómez

Gamazo

Román

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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Background: Specific immunotherapy implies certain drawbacks which could be minimized by the use of good adjuvants, capable of amplifying the appropriate immune response with minimal adverse effects.Objective: To evaluate the adjuvant capacity of the association of the rough lipopolysaccharide of Brucella ovis with Gantrez ® AN nanoparticles.Methods: Ovalbumin (allergen model)-containing Gantrez ® AN nanoparticles with either encapsulated or coated lipopolysaccharide were prepared and administered intradermally to BALB/c mice in order to evaluate the immune response. Pre-sensitized BALB/c mice were also administered with the formulations and they were challenged with an intraperitoneal injection of ovalbumin. Anaphylactic symptoms, including mortality rates, were evaluated after the challenge.

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“…Briefly, 72 h after final challenge, mice were anaesthetized, tracheotomized and connected to the ventilator. Mechanical ventilation was carried out, dynamic airway pressure (DP) and volume of chamber (DV) were recorded, and peak resistance and compliance were automatically measured as Rrs 5 DP/(DV/DT) and Clydn 5 DV/DP after each 200 mL of intra-jugular administration of various doses of acetylcholine chloride (mg) [50].…”

Section: Plethysmographymentioning

confidence: 99%

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

et al. 2008

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Asthma is a chronic inflammatory disorder caused by T-cell-mediated inflammation within airways. No antigen-specific treatment has been available. Using an OVA-induced murine asthma model, we find that co-immunization of an OVA epitope peptide with a DNA vaccine encoding the same epitope is able to prevent this experimental asthma as evidenced in the marked reduction of infiltrations of eosinophils and lymphocytes into the site of the allergen challenge. We demonstrate that the prevention of experimental asthma was directly related to the induction of a population of OVA-specific T-regulatory cells (Treg) exhibiting a CD4 1 CD25 À FoxP3 1 phenotype and expressing IL-10, TGF-b and IFN-c following the co-immunization. Blockade of IL-10 and TGF-b of the Treg by anti-IL-10 and TGF-b antibodies is partially able to reverse the suppression in vitro and in vivo, which caused the recurrence of the inflammation. Furthermore, adoptive transfer of the induced Treg is also able to suppress the OVA-induced asthma. To our knowledge, the combination of peptide with its cognate DNA vaccine protect experimental asthma via the induced epitope-specific Treg has not been previously reported and such strategy may lead to a novel immunotherapy against asthma in humans.Key words: Asthma Á Immune regulation Á Tolerance Á Treg cell Á Vaccination IntroductionAsthma is a chronic inflammatory disorder of the airways characterized by airway obstruction, increased airway responsiveness to a variety of stimuli as well as the infiltration by many inflammatory cells, including eosinophils, macrophages, lymphocytes and mast cells into lung tissue. CD4 1 T cells and Th2-biased cytokines (i.e. IL-4, IL-5 and IL-13) are believed to play a central role in the initiation and maintenance of the asthmatic response by regulating the production of IgE and the differentiation, recruitment and activation of mast cells and eosinophils [1][2][3].It has been proposed that Th1 cells, which secrete interferon-g (IFN-g), could protect against allergic disease by inhibiting the proliferation and development of Th2 cells [4] and IgE production [5]. Approaches of redirecting immunity from a Th2 type to Th1 type have also been demonstrated to result in temporary reduction of allergic reactions [6]. However, both autoimmune disease [7] and pathogen infection [8] induced Th1-biased immune responses were found to reduce the likelihood of allergy disease. Hansen et al. demonstrated that antigen-specific Th1 cells were ineffective in reducing the airway hyper-reactivity induced by Th2 cells but caused serious airway inflammation [9]. Thus, immunotherapeutic approaches using Th1 cell responses against asthma are rather complicated.Besides redirecting immunity-based approaches, several other strategies have also been considered to reduce allergic responses, including non-specific immunosuppressive drugs or monoclonal [21,22]. In this report, we further demonstrated that co-immunization of DNA and peptide vaccines against the same epitope-sequence of ovalbumin (OVA, aa 323...

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TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway

Cited by 85 publications

References 41 publications

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis

Protein/DNA vaccine‐induced antigen‐specific Treg confer protection against asthma

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