NLRP3 inflammasome activation in aged macrophages is diminished during Streptococcus pneumoniae infection

Soo Jung Cho, Kristen Rooney, Augustine M.K. Choi, Heather W. Stout-Delgado

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Pneumococcal infections are the eigth leading cause of death in the United States, and it is estimated that older patients (≥65 yr of age) account for the most serious cases. The goal of our current study is to understand the impact of biological aging on innate immune responses to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. With the use of in vitro and in vivo aged murine models, our findings demonstrate that ageenhanced unfolded protein responses (UPRs) contribute to diminished inflammasome assembly and activation during S. pneumoniae infection. Pretreatment of aged mice with endoplasmic reticulum chaperone and the stress-reducing agent tauroursodeoxycholic acid (TUDCA) decreased mortality in aged hosts that was associated with increased NLRP3 inflammasome activation, improved pathogen clearance, and decreased pneumonitis during infection. Taken together, our data provide new evidence as to why older persons are more susceptible to S. pneumoniae and provide a possible therapeutic target to decrease morbidity and mortality in this population.

Original languageEnglish (US)
Pages (from-to)L372-L387
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume314
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Aging
  • ER stress
  • Inflammasome
  • Macrophage
  • Pneumonia

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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