Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-Mediated IFN-β production during streptococcus pneumoniae infection Academic Article uri icon

Overview

MeSH Major

  • Aging
  • Endoplasmic Reticulum Stress
  • Interferon-beta
  • Membrane Proteins
  • Pneumococcal Infections

abstract

  • Pneumococcal infections remain a leading cause of death in persons ≥ 65 y of age. Recent reports have illustrated detrimental changes in the endoplasmic reticulum stress response or unfolded protein response in aging and age-related diseases; however, the relationship between aging, the unfolded protein response, and innate immune responses to Streptococcus pneumoniae has not been fully elucidated. Our results illustrate that stimulator of IFN genes-mediated production of IFN-β during S. pneumoniae infection is decreased in aged hosts. Enhanced endoplasmic reticulum stress in response to S. pneumoniae augmented inositol-requiring protein 1/X-box binding protein 1-mediated production of autophagy-related gene 9 (Atg9a). Knockdown of Atg9a or treatment with gemcitabine HCl resulted in enhanced stimulator of IFN genes-mediated production of IFN-β by aged macrophages. Consecutive treatments with gemcitabine during in vivo S. pneumoniae infection decreased morbidity and mortality in aged hosts, which was associated with decreased Atg9a expression, increased IFN-β production, and improved bacterial clearance from lung tissue. Taken together, data presented in this study provide new evidence as to why older persons are more susceptible to S. pneumoniae, and provide a possible mechanism to enhance these responses, thereby decreasing morbidity and mortality in this population.

publication date

  • May 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4007355

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1303090

PubMed ID

  • 24670807

Additional Document Info

start page

  • 4273

end page

  • 83

volume

  • 192

number

  • 9