Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection.

Authors: Warren, Rachel; Domm, William; Yee, Min; Campbell, Andrew; Malone, Jane; Wright, Terry; Mayer-Pröschel, Margot; O'Reilly, Michael A

Published In Am J Physiol Lung Cell Mol Physiol, (2019 11 01)

Abstract: 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.

PubMed ID: 31509427 Exiting the NIEHS site

MeSH Terms: Animals; Ataxia Telangiectasia Mutated Proteins/physiology; CD8-Positive T-Lymphocytes/immunology*; CD8-Positive T-Lymphocytes/metabolism; CD8-Positive T-Lymphocytes/virology; Immunologic Memory/immunology*; Influenza A virus/immunology*; Lung/immunology*; Lung/metabolism; Lung/virology; Mice; Mice, Knockout; Mutation*; Orthomyxoviridae Infections/immunology*; Orthomyxoviridae Infections/metabolism; Orthomyxoviridae Infections/virology

Back
to Top