Enhancement of Immune Memory Response to Respiratory Infection
Abstract
Influenza infection claims around half million lives around the world each year, while World Health Organization estimates put the yearly cost of influenza infection to the US economy at over $100 billion. Despite advances in modern medicine, production of protective antibodies against viral infection remains the most effective strategy to prevent morbidity and mortality. Maintenance of long-term immune cell memory against influenza virus is the basis for most currently available immunizations. However, whether and how immune cells in smokers fail to form memory cells is unclear. We have recently found that a particular family of genes involved in immune cells called “autophagy gene” are highly expressed in white blood cells including B lymphocytes that are responsible for producing antibodies against influenza virus. In mice, autophagy 7 is required for the maintenance of protective B-lymphocytes (memory B cells) needed to fight against influenza infection. Mice with B cell-specific deficiency in autophagy 7 show accelerated memory B cell death after immunization with influenza and succumb to influenza infection due to failure to generate protective secondary antibody responses. Human influenza-specific memory B cells also have high levels of autophagy, but whether autophagy protects memory B cell survival in mice exposed to smoke or humans remains unknown. Further, chronic obstructive pulmonary disease (COPD) exacerbation due to influenza results in large number of hospitalization and increased mortality in smokers even if they routinely receive the vaccine. The goals of this application are to determine the cellular and molecular mechanisms responsible for the maintenance of memory B cells against influenza, and to explore novel means to boost autophagy in memory B cells and the production of neutralizing antibody in smokers with COPD that are vulnerable to influenza infection. Our findings will facilitate the development of improved strategies to protect against influenza infection in normal and in highly vulnerable populations such as smokers with COPD by promoting autophagy. The proposed study has direct relevance to the healthcare needs of military Service members, Veterans, and beneficiaries, who are at greater risks to be exposed to influenza and other respiratory infectious agents. Our work may also provide a mechanistic frame for other investigators who are studying immune cells against other respiratory viruses, bacteria, parasites, and cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010607
Entities
People
- Farrah Kheradmand
Organizations
- Baylor College of Medicine
- United States Army