Toll/IL-1 Signaling Is Critical for House Dust Mite–specific Th1 and Th2 Responses

Phipps, Simon; Lam, Chuan En; Kaiko, Gerard E.; Foo, Shen Yun; Collison, Adam; Mattes, Joërg; Barry, Jessica; Davidson, Sophia; Oreo, Kevin; Smith, Lauren; Mansell, Ashley; Matthaei, Klaus I.; Foster, Paul S.

doi:10.1164/rccm.200806-974oc

Cited by 149 publications

(135 citation statements)

References 60 publications

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“…This is in contrast to airway neutrophilia that disappeared completely in our model (consistent with Ref. 37) and the MyD88 dependency of allergic responses observed after house dust mite challenge, intranasal challenge of OVA with low-dose LPS, or in the presence of bacterial infection (29,55,56).…”

Section: Discussionsupporting

confidence: 88%

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

Robays

Lanckacker

Moerloose

et al. 2009

The Journal of Immunology

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Cigarette smoking is associated with the development of allergic asthma. In mice, exposure to cigarette smoke sensitizes the airways toward coinhaled OVA, leading to OVA-specific allergic inflammation. Pulmonary dendritic cells (DCs) are professional APCs involved in immunosurveillance and implicated in the induction of allergic responses in lung. We investigated the effects of smoking on some of the key features of pulmonary DC biology, including trafficking dynamics and cellular activation status in different lung compartments. We found that cigarette smoke inhalation greatly amplified DC-mediated transport of inhaled Ags to mediastinal lymph nodes, a finding supported by the up-regulation of CCR7 on airway DCs. Pulmonary plasmacytoid DCs, which have been involved in inhalational tolerance, were reduced in number after smoke exposure. In addition, combined exposure to cigarette smoke and OVA aerosol increased surface expression of MHC class II, CD86, and PDL2 on airway DCs, while ICOSL was strongly down-regulated. Although inhaled endotoxins, which are also present in cigarette smoke, have been shown to act as DC activators and Th2-skewing sensitizers, TLR4-deficient and MyD88 knockout mice did not show impaired eosinophilic airway inflammation after concomitant exposure to cigarette smoke and OVA. From these data, we conclude that cigarette smoke activates the pulmonary DC network in a pattern that favors allergic airway sensitization toward coinhaled inert protein. The TLR independency of this phenomenon suggests that alternative immunological adjuvants are present in cigarette smoke.

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Section: Discussionsupporting

confidence: 88%

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

Robays

Lanckacker

Moerloose

et al. 2009

The Journal of Immunology

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“…Total IgE serum levels were measured by means of ELISA (Bethyl Laboratories, Montgomery, TX), according to the manufacturer's protocol. For the measure of allergen-specific IgE, IgG1, and IgG2a, we used a previously reported protocol (31). Briefly, 96-well plates were coated overnight at 4˚C with allergen (HDM or OVA) or unlabeled anti-IgE, IgG1, and IgG2a (SouthernBiotech, Birmingham, AL) of corresponding isotype for standard wells.…”

Section: Protein Extraction and Analysismentioning

confidence: 99%

Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12

Paulissen

Hour

Rocks

et al. 2012

The Journal of Immunology

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A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue remodeling associated with pathological processes. Among them, ADAMTS12 was identified as an asthma-associated gene in a human genome screening program. However, its functional implication in asthma is not yet documented. The present study aims at investigating potential ADAMTS-12 functions in experimental models of allergic airways disease. Two different in vivo protocols of allergen-induced airways disease were applied to the recently generated Adamts12-deficient mice and corresponding wild-type mice. In this study, we provide evidence for a protective effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In the absence of Adamts12, challenge with different allergens (OVA and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cell counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen-challenged Adamts12-deficient mice. The present study provides, to our knowledge, the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in airways disease, interfering with immunological processes leading to inflammation and airway hyperresponsiveness.

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“…TLR4 signaling was shown to be required to modulate allergic responses in several animal model studies. 29,30 TLR4-deficient mice showed decreased ovalbumin-induced eosinophilic inflammation in the lung, allergen-specific IgE levels, and Th2 cytokine production compared with wild-type controls. We observed a significantly lower sensitization rate to wheat flour on SPT in carriers of TLR4 variants.…”

Section: Discussionmentioning

confidence: 94%

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Cho

Kim

et al. 2011

Annals of Allergy, Asthma & Immunology

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Toll/IL-1 Signaling Is Critical for House Dust Mite–specific Th1 and Th2 Responses

Abstract: Together, these data suggest that Th2- and Th17-mediated inflammation generated on inhalational HDM exposure is differentially regulated by the presence of microbial products and the activation of distinct MyD88-dependent pattern recognition receptors.

Cited by 149 publications

References 60 publications

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

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