The house dust mite allergen Der p 5 binds lipid ligands and stimulates airway epithelial cells through a TLR2‐dependent pathway

Pulsawat, Pinya; Soongrung, Tewarit; Satitsuksanoa, Pattraporn; Mignon, Maxime Le; Khemili, Souad; Gilis, Dimitri; Nony, Emmanuel; Kennedy, Malcolm W.; Jacquet, Alain

doi:10.1111/cea.13278

Cited by 31 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HDM contains over 20 allergens that affect airway structural barriers, inducing innate cytokines such as IL‐25, IL‐33 and TSLP, which then initiate allergic inflammation. Although TLR2 seems not to be mainly involved in the phenotype of the HDM‐induced asthma model, HDM can activate TLR2 on various cell types and induce release of inflammatory cytokines . Our study implicated HDM activated TLR2 only in PAM‐stimulated ILC2s to augment asthmatic phenotype.…”

Section: Discussionmentioning

confidence: 58%

“…Although TLR2 seems not to be mainly involved in the phenotype of the HDM-induced asthma model, 25 HDM can activate TLR2 on various cell types and induce release of inflammatory cytokines. 26,27 Our study implicated HDM activated TLR2 only in PAM-stimulated ILC2s to augment asthmatic phenotype. Among HDM allergens, Der p 13 can bind fatty acid and induce TLR2-associated immune response.…”

Section: F I G U R E 5 Evaluation Of Contribution Of B Cells and T Cementioning

confidence: 75%

See 1 more Smart Citation

Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics

Ishii

Muroi

Horiguchi

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

Background Type 2 innate lymphoid cells (ILC2s) are one of the sources of IL‐5 and IL‐13 in allergic airway inflammation. Innate immune receptors such as Toll‐like receptors (TLRs) expressed on epithelial cells could contribute to ILC2 activation through IL‐33 production, but a direct effect of TLRs on ILC2s remains to be elucidated. Objectives We hypothesized that TLRs can directly activate lung ILC2s and participate in the pathogenesis of asthma. Methods After intranasal administration of IL‐33 to wild‐type (WT), TLR2KO and TLR4KO female mice, ILC2s were isolated from harvested lungs. ILC2s were incubated with IL‐2 and TLR stimulants (pam3csk4 (PAM), house dust mite extract (HDM)). In some experiments, TLR2 or dectin‐1 signalling inhibitors were used. As an in vivo model, the mice were treated with IL‐33 and rested until lung recruitment of eosinophils regressed. Then they were treated intranasally with PAM + HDM or vehicle and analysed. Results In vitro stimulation of isolated ILC2s showed that PAM could induce IL‐13 and IL‐5 production, and HDM had a synergistic effect on this stimulation. Both effects were dependent on TLR2 and NF‐κB signalling. PAM + HDM stimulation of WT mice led to increased ILC2s, airway hyperresponsiveness and increased levels of both neutrophils and eosinophils in bronchoalveolar lavage fluid. These observations were dependent on TLR2. Conclusions & clinical relevance TLR2 can directly activate lung ILC2s, an effect that is augmented by HDM. Asthmatic characteristics mediated through the TLR2 pathway were evident in the in vivo mice model. These data implicate a new pathway of ILC2 activation in the pathogenesis of asthma.

show abstract

Section: Discussionmentioning

confidence: 58%

Section: F I G U R E 5 Evaluation Of Contribution Of B Cells and T Cementioning

confidence: 75%

Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics

Ishii

Muroi

Horiguchi

et al. 2019

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…[23][24][25][26][27][28][29] These characteristics could influence the clinical impact of each allergen but may not correlate with the frequency of IgE binding. This could be the case for Der p 13 18 ; Der p 18 30,31 ; Der p 7 31 ; Der p 5 32 ; other proteases such as Der p 3, Der p 6, and Der p 9 33 ; and other lipid-binding proteins such as Der p 21 and Blo t 13. Therefore, in some cases, the IgE binding detected by PAMD@ might be considered a proxy for more crucial allergenic properties.…”

Section: New Concepts Regarding the Mechanisms Of Action Of Allergensmentioning

confidence: 98%

A WAO — ARIA — GA2LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020

Ansotegui¹,

Melioli²,

Canonica³

et al. 2020

World Allergy Organization Journal

View full text Add to dashboard Cite

Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@. PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies.

show abstract

“…Der p 5 binds lipids under mildly acidic conditions (as found in the mite midgut) in monomeric form also, 74,76,77 and through such cargo activates TLR2-NFκB-mitogen-activated protein kinase (MAPK)-dependent signalling in airway epithelial cells. 77…”

Section: Group 5 and Group 21 Hdm Allergens And Tlr2mentioning

confidence: 99%

“…In the dimeric form revealed by X‐ray crystallography, an interfacial hydrophobic pocket is formed between the monomers, offering potential ligation of lipids and facilitation of interactions with TLRs . In spite of this, recombinant Der p 5 binds lipids under mildly acidic conditions (as found in the mite midgut) in monomeric form also, and through such cargo activates TLR2‐NFκB‐mitogen‐activated protein kinase (MAPK)–dependent signalling in airway epithelial cells . Analogous evidence exists for Der p 21 …”

Section: Hdm Allergens and Toll‐like Receptorsmentioning

confidence: 99%

Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens

Jacquet

Robinson

2019

Allergy

Self Cite

View full text Add to dashboard Cite

House dust mites (HDMs) are sources of an extensive repertoire of allergens responsible for a range of allergic conditions. Technological advances have accelerated the identification of these allergens and characterized their putative roles within HDMs. Understanding their functional bioactivities is illuminating how they interact with How to cite this article: Jacquet A, Robinson C. Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens. Allergy.

show abstract

The house dust mite allergen Der p 5 binds lipid ligands and stimulates airway epithelial cells through a TLR2‐dependent pathway

Abstract: Despite the fact that Der p 5 represents a HDM allergen of intermediate prevalence, our findings regarding its lipid binding and activation of TLR2 indicate that it could participate in the initiation of the HDM-allergic state.

Cited by 31 publications

References 44 publications

Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics

Activation through toll‐like receptor 2 on group 2 innate lymphoid cells can induce asthmatic characteristics

A WAO — ARIA — GA2LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020

Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens

Contact Info

Product

Resources

About