Mitochondrial Dysfunction in Aged Macrophages and Lung during Primary Streptococcus pneumoniae Infection is Improved with Pirfenidone
Open accessAbstract
Pneumococcal infections remain a leading cause of death in older adults, with the most serious cases occurring in persons ≥65 years of age. There is an urgent need to investigate molecular pathways underlying these impairments and devise new therapeutics to modulate innate immunity. The goal of our current study is to understand the impact of chronological aging on mitochondrial function in response to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using chronologically aged murine models, our findings demonstrate that decreased ATP production is associated with dysregulated mitochondrial complex expression, enhanced oxidative stress, diminished antioxidant responses, and decreased numbers of healthy mitochondria in aged adult macrophages and lung in response to S. pneumoniae. Pre-treatment of aged macrophages with pirfenidone, an anti-fibrotic drug with antioxidant and anti-inflammatory properties, improved mitochondrial function and decreased cellular oxidative stress responses. In vivo administration of pirfenidone decreased superoxide formation, increased healthy mitochondria number, improved ATP production, and decreased inflammatory cell recruitment and pulmonary oedema in aged mouse lung during infection. Taken together, our data shed light on the susceptibility of older persons to S. pneumoniae and provide a possible therapeutic to improve mitochondrial responses in this population.
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Experimental studies have illustrated an age-associated increase in ROS levels that corresponds with decreased antioxidative responses in AM.
“Experimental studies have illustrated an age-associated increase in ROS levels that corresponds with decreased antioxidative responses in AM (111, 112).”
From Aging and Lung Disease (2020) · cites this paper as [111]
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- Authors
- Plataki, M., Cho, S. J., Harris, R. M., Huang, H.-R., Yun, H. S., Schiffer, K. T., & Stout-Delgado, H. W.
- Affiliations
- Weill Cornell Medicine (US)
- Corresponding author
- Stout-Delgado, Heather W.
- Venue
- Scientific Reports
- Published
- 2019-01-30
- Volume
- 9
- Issue
- 1
- Pages
- 971-971
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6353918
- OpenAlex
- W2912699349
- Cited by
- 42
- References
- 43
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 3
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- China Scholarship Council
- National Institute on Aging (R01AG056699, R21AG044755, L30 AG057058, R01AG052530, K01AG034999)
- National Heart, Lung, and Blood Institute (K08HL138285)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial dysfunction, aging, macrophages, Streptococcus pneumoniae, pirfenidone, bacterial pneumonia, oxidative stress, ATP production, innate immunity, pulmonary edema, superoxide, older adults, antifibrotic therapy
- MeSH terms
- Adenosine Triphosphate, Animals, Antioxidants, Female, Gene Expression Regulation, Lung, Macrophages, Male, Mice, Inbred BALB C, Mitochondria, Pneumococcal Infections, Pyridones, Superoxides, Cellular Senescence, Oxidative Stress, Cell Respiration, Membrane Potential, Mitochondrial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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