Diminished inflammatory responses to natural pneumovirus infection among older mice
Cynthia A Bonville1, Nicholas J Bennett, Caroline M Percopo
1Department of Pediatrics, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Abstract:
Immune responses to virus infection undergo significant change as part of the aging process. Here we examine the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators, including MIP-1alpha, JE/MCP-1, IFN-gamma and IFN-gamma-induced MIG and IP-10, and interleukins (IL)-6 and IL-17. Levels of KC and IL-1alpha remained unchanged. Age-dependent diminished production of proinflammatory mediators was associated with diminished recruitment of granulocytes and reduced severity of clinical responses, including weight loss and respiratory dysfunction. The differences observed when comparing these results to those reported among elderly human subjects may be related to the specific extent of aging and its impact on biochemical and cellular inflammatory responses and/or the role of lifetime virus re-exposure on the clinical outcome from acute pneumovirus disease.
Insights
Aging impairs immune responses to pneumonia virus of mice (PVM) infection. Older mice showed reduced inflammatory mediators and immune cell recruitment, leading to less severe illness, unlike some human aging patterns.
Area of Science:
- Immunology
- Virology
- Gerontology
Background:
- Immune responses to viral infections change with age.
- Aging can impact the body's ability to fight off pathogens effectively.
Purpose of the Study:
- To investigate the inflammatory response in older, immunologically naive mice infected with pneumonia virus of mice (PVM).
- To understand how aging affects local mediator production and immune cell recruitment during viral pneumonia.
Main Methods:
- Infection of older mice with PVM.
- Measurement of inflammatory mediators (cytokines, chemokines) in lung tissue.
- Assessment of immune cell infiltration (granulocytes).
- Monitoring of clinical signs like weight loss and respiratory function.
Main Results:
- No significant changes in PVM replication extent or kinetics were observed.
- Diminished local production of key inflammatory mediators, including MIP-1alpha, JE/MCP-1, IFN-gamma, MIG, IP-10, IL-6, and IL-17.
- Unchanged levels of KC and IL-1alpha.
- Reduced granulocyte recruitment and less severe clinical symptoms (weight loss, respiratory dysfunction).
Conclusions:
- Age-dependent reduction in inflammatory mediators correlates with impaired immune cell recruitment and milder clinical outcomes in PVM-infected mice.
- Differences from human studies may stem from varying aging extents or prior virus exposure.
- This study provides insights into age-related immune dysregulation during acute viral respiratory infections.
