tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol. 2019 Sep 11. doi: 10.1152/ajplung.00031.2019. [Epub ahead of print]
[h=1]Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection.[/h] Warren R[SUP]1[/SUP], Domm W[SUP]2[/SUP], Yee M[SUP]3[/SUP], Campbell A[SUP]4[/SUP], Malone J[SUP]2[/SUP], Wright T[SUP]2[/SUP], Mayer-Proschel M[SUP]5[/SUP], O'Reilly MA[SUP]2[/SUP].
[h=3]Author information[/h] 1 Microbiology and Immunology, The University of Rochester, United States. 2 Pediatrics, The University of Rochester, United States. 3 Pediatrics, University of Rochester, United States. 4 Biomedical Genetics, The University of Rochester, United States. 5 University of Rochester.
[h=3]Abstract[/h] 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 lower levels of select serum antibodies to IAV hemagglutinin (HA)-specific compared to WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection implying that vaccination of A-T children by itself may not be sufficiently protective against respiratory viral infections.
[h=4]KEYWORDS:[/h] ataxia telangiectasia; immune memory; influenza A virus; recurrent infections; vaccination
PMID: 31509427 DOI: 10.1152/ajplung.00031.2019
[h=1]Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection.[/h] Warren R[SUP]1[/SUP], Domm W[SUP]2[/SUP], Yee M[SUP]3[/SUP], Campbell A[SUP]4[/SUP], Malone J[SUP]2[/SUP], Wright T[SUP]2[/SUP], Mayer-Proschel M[SUP]5[/SUP], O'Reilly MA[SUP]2[/SUP].
[h=3]Author information[/h] 1 Microbiology and Immunology, The University of Rochester, United States. 2 Pediatrics, The University of Rochester, United States. 3 Pediatrics, University of Rochester, United States. 4 Biomedical Genetics, The University of Rochester, United States. 5 University of Rochester.
[h=3]Abstract[/h] 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 lower levels of select serum antibodies to IAV hemagglutinin (HA)-specific compared to WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection implying that vaccination of A-T children by itself may not be sufficiently protective against respiratory viral infections.
[h=4]KEYWORDS:[/h] ataxia telangiectasia; immune memory; influenza A virus; recurrent infections; vaccination
PMID: 31509427 DOI: 10.1152/ajplung.00031.2019