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Updated: Aug 19, 2026

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Aging and PMN response to P. aeruginosa infection
K A Kernacki1, R P Barrett, S A McClellan
1Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Purpose:
Alterations in immune system function associated with aging may contribute to increased morbidity in this population of individuals. The current studies were performed to determine aging-related changes in polymorphonuclear neutrophil (PMN) function after corneal infection with Pseudomonas aeruginosa.
Methods:
Total PMN number, macrophage inflammatory protein (MIP)-2 mRNA and protein expression, and ocular bacterial load were determined in 8-week- and 12-month-old inbred BALB/c mice at various times after infection with P. aeruginosa. In addition, 12-month-old mice were treated systemically with the MIP-2 polyclonal antibody (pAb) to determine the effects of MIP-2 neutralization on ocular disease and PMN recruitment.
Results:
Histologically, PMN infiltration into the cornea of 12-month-old mice was delayed initially and was associated with an inability to reduce bacterial load at later postinfection (PI) times. In addition, a significantly greater number of PMNs were found in the cornea of 12-month-old mice at later PI times. The increase in PMN number in 12-month-old mice correlated with a persistence of MIP-2 expression in cornea at these later times. Systemic treatment of 12-month-old mice with neutralizing MIP-2 pAb versus normal rabbit serum (NRS) resulted in reduced corneal PMN number and ocular disease.
Conclusions:
These data provide evidence that persistence of PMN in the cornea of 12-month-old mice contributes to corneal tissue destruction after P. aeruginosa challenge. Further evidence also is provided that the chemoattractant MIP-2 contributes to the altered PMN response in these animals.
Insights
Aging impairs polymorphonuclear neutrophil (PMN) function, leading to delayed bacterial clearance and increased corneal damage after Pseudomonas aeruginosa infection. Macrophage inflammatory protein-2 (MIP-2) neutralization mitigates these aging-related immune deficits.
Area of Science:
- Immunology
- Ophthalmology
- Microbiology
Background:
- Aging is linked to immune system dysfunction, potentially increasing disease severity in older individuals.
- Polymorphonuclear neutrophils (PMNs) are critical immune cells involved in combating bacterial infections, including those affecting the cornea.
Purpose of the Study:
- To investigate aging-related alterations in PMN function following corneal infection with Pseudomonas aeruginosa.
- To determine the role of macrophage inflammatory protein-2 (MIP-2) in the aged immune response to P. aeruginosa keratitis.
Main Methods:
- Comparison of PMN number, MIP-2 expression (mRNA and protein), and bacterial load in young (8-week) and aged (12-month) BALB/c mice post-P. aeruginosa infection.
- Systemic administration of MIP-2 neutralizing antibody in aged mice to assess its impact on ocular disease and PMN recruitment.
Main Results:
- Aged mice exhibited delayed PMN infiltration and impaired bacterial load reduction in the cornea.
- Increased PMN numbers in aged corneas correlated with persistent MIP-2 expression.
- MIP-2 neutralization in aged mice reduced corneal PMN infiltration and attenuated ocular disease severity.
Conclusions:
- Persistent PMN presence in the cornea of aged mice contributes to tissue destruction after P. aeruginosa challenge.
- The chemoattractant MIP-2 plays a significant role in the altered PMN response observed in aged individuals during P. aeruginosa keratitis.
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