title: IL-1R1-MyD88 axis elicits papain-induced lung inflammation.
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.
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Rafiou
authors: R
authors: Agoro
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Julie
authors: J
authors: Piotet-Morin
authors: Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
authors: Jennifer
authors: J
authors: Palomo
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Chloé
authors: C
authors: Michaudel
authors: Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
authors: Solenne
authors: S
authors: Vigne
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Isabelle
authors: I
authors: Maillet
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Pauline
authors: P
authors: Chenuet
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Noëlline
authors: N
authors: Guillou
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Jessica
authors: J
authors: Le Bérichel
authors: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors: Malgorzata
authors: M
authors: Kisielow
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Per
authors: P
authors: Flodby
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Zea
authors: Z
authors: Borok
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Edward D
authors: ED
authors: Crandall
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Marc
authors: M
authors: Le Bert
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Valérie
authors: V
authors: Quesniaux
authors: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors: Matthias
authors: M
authors: Muller
authors: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors: Franco
authors: F
authors: Di Padova
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors: Bernhard
authors: B
authors: Ryffel
authors: Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
authors: Cem
authors: C
authors: Gabay
authors: Experimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS, UMR7355, Orleans, France. aurelie.maillard@cnrs-orleans.fr.|Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa. aurelie.maillard@cnrs-orleans.fr.
authors: Aurélie
authors: A
authors: Couturier-Maillard
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D004804:Eosinophils / Q000276:immunology; D007113:Immunity, Innate; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010206:Papain / Q000008:administration & dosage / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000067596:Interleukin-33; D053594:Myeloid Differentiation Factor 88; D010206:Papain; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; C583355:IL1R1 protein, mouse; C506535:Il33 protein, mouse; C507780:Myd88 protein, mouse; C569500:Il1rl2 protein, mouse
keywords: Eosinophilia; IL-1R1; Lung inflammation; MyD88; Papain