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

Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 11;: Authors: Warren R, Domm W, Yee M, Campbell A, Malone J, Wright T, Mayer-Proschel M, O'Reilly MA Abstract Ataxia-telangiectasia (A-T) is a neurodegenerative disorder affecting approximately 1 in 40,000 to 100,000 children caused by mutations in the A-T mutated(ATM) gene. Recurrent respiratory infections are a common and challenging co-morbidity often leading to the development of bronchiectasis in A-T individuals. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wildtype (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 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, Atm-null mice had significantly ...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research