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

American Journal of Physiology. Lung Cellular and Molecular Physiology
Soo Jung ChoHeather W Stout-Delgado

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 age-enhanced 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.

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Citations

Aug 31, 2019·International Journal of Molecular Sciences·Noemi BorsaMarcos I Restrepo
Jul 11, 2018·Frontiers in Immunology·Lavida R K Brooks, George I Mias
Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty
Nov 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Soo Jung ChoHeather W Stout-Delgado
Dec 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark J McVeyNeil M Goldenberg
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Methods Mentioned

BETA
transfection
PCR
ELISA
protein assay
coimmunoprecipitation
electrophoresis
nuclear translocation
protein folding
Profiler

Software Mentioned

PathScan
Multi
GraphPad prism
Gauge

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