biostudies-literatureMitzel DNNIA NIH HHS4273-83https://www.ebi.ac.uk/biostudies/studies/S-EPMC4007355biostudies-literatureUnknown192(9)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 enhancJournal of immunology (Baltimore, Md. : 1950)Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-mediated IFN-β production during Streptococcus pneumoniae infection.PMC4007355K01 AG034999L30 AG043118R21AG044755K01AG034999R21 AG044755Liu YMitzel DNShirali ACLowry VStout-Delgado HWfalseAge-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-mediated IFN-β production during Streptococcus pneumoniae infection.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 enhanc2014-01-01T00:00:00Z2014 May2025-04-21T18:58:48.525Z2019-03-27T01:27:27ZS-EPMC40073552467080710.4049/jimmunol.1303090