Uric acid pathway activation during Respiratory virus infection promotes Th2 immune responses via innate cytokine production and ILC2 accumulation
| Autor: | Antonia P. Popova, Charles F. Schuler, Tracy X. Cui, Andrew J. Rasky, Nicholas W. Lukacs, Carrie-Anne Malinczak, Shannon K.K. Best, Wendy Fonseca, Susan B. Morris |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Thymic stromal lymphopoietin medicine.medical_treatment Immunology Respiratory Mucosa Respiratory Syncytial Virus Infections CCL2 Article Pathogenesis 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Th2 Cells Immunopathology medicine Immunology and Allergy Animals Humans Innate immune system business.industry Macrophages respiratory system Immunity Innate Respiratory Syncytial Viruses Uric Acid Disease Models Animal 030104 developmental biology Cytokine chemistry Uric acid Cytokines Female Lymph Nodes Inflammation Mediators business Metabolic Networks and Pathways 030215 immunology Signal Transduction |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | Respiratory syncytial virus (RSV) infects a majority of infants and can cause severe disease leading to increased risk to develop asthma later in life. In the present studies we detected high levels of uric acid pathway components during RSV infection and examined whether they altered the pathogenesis of RSV infection. Inhibition of uric acid (UA) pathway activation during RSV infection in airway epithelial cells using XOI decreased the expression of IL-33, thymic stromal lymphopoietin (TSLP), and CCL2. In addition, treatment of RSV infected bone marrow-derived macrophages with XOI decreased production of IL-1β. Thus, UA activation of different cell populations contributes different innate immune mediators that promote immunopathogenesis. When mice were treated with XOI or interleukin-1 receptor antagonist (IL1-ra) during RSV infection decreased pulmonary mucus was observed along with significantly reduced numbers of ILC2 and macrophages, accompanied by decreased IL-33 in bronchoalveolar lavage of the treated mice. These findings provide mechanistic insight into the development of RSV immunopathology and indicate that xanthine metabolites and UA are key immunoregulator molecules during RSV infection. Moreover, these findings suggest uric acid and IL-1β as possible therapeutic targets to attenuate severe RSV disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink