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Host Aging Induces a Senescent-Like Phenotype in Neutrophils and Altered Transcriptional Responses to Streptococcus pneumoniae - PubMed

8 hours ago
  • #aging
  • #neutrophils
  • #pneumonia
  • Aging increases susceptibility to respiratory infections by Streptococcus pneumoniae.
  • Polymorphonuclear leukocytes (PMNs) are crucial for bacterial clearance but their function declines with age.
  • RNA sequencing revealed significant transcriptomic differences in PMNs between young and old mice infected with S. pneumoniae.
  • PMNs from aged hosts failed to upregulate glycolysis and mitochondrial ROS production, essential for bacterial killing.
  • Aged PMNs exhibited higher senescence-associated secretory phenotype (SASP) scores and upregulated cellular senescence pathways.
  • Uninfected aged PMNs showed higher levels of SASP factors (IL-10, TNFα, ROS), lower apoptosis, and more senescence-associated β-galactosidase-positive cells.
  • Blocking TNFα improved PMN antibacterial activity and host resistance to S. pneumoniae in aged mice.
  • Aging shifts PMNs toward a senescent-like, energy-deficient phenotype, impairing host defense.