Essential role for autophagy in the maintenance of immunological memory against influenza infection

 Chen M., Hong M.J., Sun H., Wang L., Shi X., Gilbert B.E., Corry D.B., Kheradmand F., Wang J. Nature medicine (2014) 20 (5): 503-510

Speaker: Po-Jung Fu (傅柏蓉)                                 )                                                 Time: 13:00~14:00, Oct 29, 2014.

Commentator: Dr. Shun-hua Chen (陳舜華 老師)                 )          Place: Room 601

Abstract:

Influenza viruses containing three distinct viral types A, B and C are negative single-stranded RNA viruses of the family Orthomyxoviridae, which cause annual epidemic and sometime pandemic infection. Type A virus may infect and cause disease among human and animals [1]. Vaccination is the effective way to provide humoral-immunity protection, especially for those vulnerable one, such as children, pregnant women, elderly people and immune-comprise patients. Currently, the licensed vaccines are normalized for the hemagglutinin (HA) antigen of two influenza A strains (H1N1 and H3N2) and one or two B virus strains (Victoria and Yamagata lineage) [2]. Autophagy is a cell degradative process which maintains hemostasis and also participates in immunity. Previous study revealed that autophagy deficiency increase susceptibility to infection with Listeria monocytogenes and the protozoan Toxoplasma gondii [3]. During autophagy process, several autophagy-related genes are recruited. For example, an E1-like enzyme Atg7 activates Atg12, which is then transferred to Atg10 and conjugated to Atg5 to form an autophagosomalprecursor. In this paper, the authors generated the knock-out mice with B-cell specific deletion of Atg7 (B/Atg7^-/-) to investigate the role of autophagy in immune cell. By immunizing the B/Atg7^-/-mice with the influenza virus (A/Hong Kong/8/68), the authors found that autophagy deficiency does not affect primary antibody production. However, these mice showed defective secondary antibody response and resulted in high viral load, widespread lung destruction and increased fatality. Further investigation revealed that the defective secondary antibody response were due to oxidative stress. Autophagosome fusion with the lysosome is the major degradative pathway for mitochondrial turnover, which is responsible for eliminating excess reactive oxygen species (ROS) produced by mitochondria metabolism [4]. Since lacking of proper autophagic function, ROS was accumulated in the memory B cells and leads to cell death and defective secondary antibody response in mice. In conclusion, autophagy is essential for the survival of memory B cells and generating effective secondary antibody response.

References:

1. Nelson M.I. and Holmes E.C., The evolution of epidemic influenza. Nat. Rev. Genet. (2007) 8(3): 196-205

2. Schotsaert, M. and Garcia-Sastre A., Influenza Vaccines: A Moving Interdisciplinary Field. Viruses (2014) 6(10): 3809-3826

3. Kim, I., Rodriguez-Enriquez S., and Lemasters J.J., Selective degradation of mitochondria by mitophagy. Arch. Biochem. Biophys. (2007) 462(2): 245-53

4. Levine, B., Mizushima N., and Virgin H.W., Autophagy in immunity and inflammation. Nature (2011) 469(7330): 323-335