Inflammasome activation is required for human rhinovirus-induced airway inflammation in naive and allergen-sensitized mice
| Autor: | Caitlin R. Jarman, Toby C. Lewis, Jing Lei, Marc B. Hershenson, Charu Rajput, J. Kelley Bentley, Tomoko Ishikawa, Mark J. Hoenerhoff, Mingyuan Han, Julie Lee, Adam M. Goldsmith, William T. Jackson |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Rhinovirus Inflammasomes Interleukin-1beta Immunology Inflammation medicine.disease_cause Article Mice 03 medical and health sciences 0302 clinical medicine In vivo NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans Immunology and Allergy Receptor Respiratory Tract Infections Picornaviridae Infections Innate immune system Chemistry Pyroglyphidae Inflammasome Allergens Toll-Like Receptor 2 Disease Models Animal TLR2 030104 developmental biology Immunization medicine.symptom 030215 immunology medicine.drug |
| Zdroj: | Mucosal Immunol |
| ISSN: | 1933-0219 |
| Popis: | Activation of the inflammasome is a key function of the innate immune response that regulates inflammation in response to microbial substances. Inflammasome activation by human rhinovirus (RV), a major cause of asthma exacerbations, has not been well studied. We examined whether RV induces inflammasome activation in vivo, molecular mechanisms underlying RV-stimulated inflammasome priming and activation, and the contribution of inflammasome activation to RV-induced airway inflammation and exacerbation. RV infection triggered lung mRNA and protein expression of pro-IL-1β and NLRP3, indicative of inflammasome priming, as well as cleavage of caspase-1 and pro-IL-1β, completing inflammasome activation. Immunofluorescence staining showed IL-1β in lung macrophages. Depletion with clodronate liposomes and adoptive transfer experiments showed macrophages to be required and sufficient for RV-induced inflammasome activation. TLR2 was required for RV-induced inflammasome priming in vivo. UV irradiation blocked inflammasome activation and RV genome was sufficient for inflammasome activation in primed cells. Naive and house dust mite-treated NLRP3-/- and IL-1β-/- mice, as well as IL-1 receptor antagonist-treated mice, showed attenuated airway inflammation and responsiveness following RV infection. We conclude that RV-induced inflammasome activation is required for maximal airway inflammation and hyperresponsiveness in naive and allergic mice. The inflammasome represents a molecular target for RV-induced asthma exacerbations. |
| Databáze: | OpenAIRE |
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