Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection
| Autor: | William Domm, Min Yee, Jane E. Malone, Andrew Campbell, Rachel Warren, Terry W. Wright, Margot Mayer-Pröschel, Michael A. O'Reilly |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Recurrent infections Physiology Ataxia Telangiectasia Mutated Proteins CD8-Positive T-Lymphocytes Immunological memory medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine Orthomyxoviridae Infections Physiology (medical) Influenza A virus Animals Ataxia telangiectasia mutated Medicine Recurrent respiratory infections Lung Gene Mice Knockout business.industry Cell Biology medicine.disease Vaccination 030104 developmental biology 030228 respiratory system Mutation Immunology Ataxia-telangiectasia business Immunologic Memory Research Article |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00031.2019 |
| Popis: | Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated ( ATM) gene, is a neurodegenerative disorder affecting ∼1 in 40,000–100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wild-type (WT) and Atm-null mice with influenza A virus (IAV; HKx31, H3N2) and interrogate the immune memory with secondary infections designed to challenge the B cell memory response with homologous infection (HKx31) and the T cell memory response with heterologous infection (PR8, H1N1). Although Atm-null mice survived primary and secondary infections, they lost more weight than WT mice during secondary infections. This enhanced morbidity to secondary infections was not attributed to failure to effectively clear virus during the primary IAV infection. Instead, Atm-null mice developed persistent peribronchial inflammation, characterized in part by clusters of B220+B cells. Additionally, levels of select serum antibodies to hemagglutinin-specific IAV were significantly lower in Atm-null than WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection, implying that vaccination of children with A-T by itself may not be sufficiently protective against respiratory viral infections. |
| Databáze: | OpenAIRE |
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