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IL-1R1-MyD88 axis elicits papain-induced lung inflammation

Agoro, Rafiou
Piotet-Morin, Julie
Michaudel, Chloé
Maillet, Isabelle
Chenuet, Pauline
Guillou, Noëlline
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Published in European Journal of Immunology. 2016, vol. 46, no. 11, p. 2531-2541
Abstract Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on inflammatory responses to a single exposure to papain and showed that intranasal administration of papain results in the recruitment of inflammatory cells, including neutrophils and eosinophils with a rapid production of IL-1α, IL-1β, and IL-33. The inflammatory response is abrogated in the absence of IL-1R1 and MyD88. To decipher the cell type(s) involved in MyD88-dependent IL-1R1/MyD88 signaling, we used new cell-specific MyD88-deficient mice and found that the deletion of MyD88 signaling in single cell types such as T cells, epithelial cells, CD11c-positive or myeloid cells leads to only a partial inhibition compared to complete absence of MyD88, suggesting that several cell types contribute to the response. Importantly, the inflammatory response is largely ST2 and IL-36R independent. In conclusion, IL-1R1 signaling via MyD88 is critical for the first step of inflammatory response to papain.
Keywords Allergens/administration & dosage/immunologyAnimalsEosinophils/immunologyImmunityInnateInterleukin-1alpha/metabolismInterleukin-1beta/metabolismInterleukin-33/metabolismLung/immunology/physiopathologyMiceMyeloid Differentiation Factor 88/deficiency/genetics/immunology/metabolismNeutrophils/immunologyPapain/administration & dosage/immunologyPneumonia/immunologyReceptorsInterleukin-1/immunology/metabolismReceptorsInterleukin-1 Type I/immunology/metabolismSignal TransductionTh2 Cells/immunology
PMID: 27569535
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Research group Mécanisme de l'inflammation articulaire (44)
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AGORO, Rafiou et al. IL-1R1-MyD88 axis elicits papain-induced lung inflammation. In: European Journal of Immunology, 2016, vol. 46, n° 11, p. 2531-2541. doi: 10.1002/eji.201646366 https://archive-ouverte.unige.ch/unige:99456

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Deposited on : 2017-11-22

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