Cellular senescence is a double-edged sword in regulating aged immune responses to influenza
Blake L Torrance1,2, Andreia N Cadar1,2, Hunter A Panier3
1UConn Center on Aging, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Abstract:
Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.
Insights
Clearing senescent cells in aged mice improved initial flu virus clearance but impaired long-term immune memory, reducing antibody production and T cell generation for future protection.
Area of Science:
- Immunology
- Gerontology
- Virology
Background:
- Senescent cells accumulate with age and contribute to chronic diseases.
- The role of senescent cells in acute infection response and immune memory formation is unclear.
- Targeting senescent cells is a potential therapeutic strategy for age-related conditions.
Purpose of the Study:
- To investigate the impact of senescent cell clearance on the immune response to influenza infection in aged mice.
- To determine how eliminating senescent cells affects the development of immunological memory.
Main Methods:
- Utilized a p16-3MR reporter mouse model for senescent cell identification and clearance.
- Administered ganciclovir (GCV) to selectively eliminate p16-expressing senescent cells.
- Assessed viral load, antibody production, and memory T cell populations post-influenza infection and challenge.
Main Results:
- Clearance of senescent cells enhanced viral clearance during primary influenza infection.
- GCV treatment led to reduced lung antibody production and fewer flu-specific CD8 memory T cells.
- GCV-treated mice showed impaired memory responses and increased viral load upon subsequent heterosubtypic challenge.
Conclusions:
- Targeting senescent cells can improve acute viral clearance in aged individuals.
- Eliminating senescent cells may compromise the formation of durable and protective immune memory.
- Therapeutic strategies involving senescent cell clearance require careful consideration of their impact on long-term immunity.
More Related Videos
07:07Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
13:59A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
Published on: August 12, 2018
Related Concept Videos
01:40Cell-mediated Immune Responses
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
01:23Cells of the Adaptive Immune Response
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:01Regulation of Hematopoietic Stem Cells