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Fig.4.A showing Flow cytometry/Cell sorting from the publication: Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.
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Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.

In GeroScience on 1 October 2022 by Connors, J., Taramangalam, B., et al.

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4+ T cell priming DCs (cDC2s), and CD14dimCD16+ vascular patrolling monocytes from older adults (n = 11) following stimulation with pathway-specific agonists in comparison with young individuals (n = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects.
© 2022. The Author(s).

  • FC/FACS
  • Homo sapiens (Human)
  • Immunology and Microbiology
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PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

In Cell Reports on 11 December 2018 by Ding, L., Kim, H. J., et al.

PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in mice bearing Brca1-deficient ovarian tumors. This effect is further augmented when olaparib is combined with PD-1 blockade. Our findings thus provide a molecular mechanism underlying antitumor activity by PARP inhibition and lay a foundation to improve therapeutic outcome for cancer patients.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  • Cancer Research
  • Immunology and Microbiology
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Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.

In Geroscience on 1 October 2022 by Connors, J., Taramangalam, B., et al.

Fig.4.A
Fig.4.A showing Flow cytometry/Cell sorting from the publication: Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists.
  • FC/FACS
Monocyte and DC subsets from older individuals are impaired in TANK-binding kinase (TBK) phosphorylation. Human PBMCs from the blood of younger (age, 24–36 years; n = 11) and older (age, 67–83 years; n = 11) healthy donors were either stimulated with LPS/IFN-γ, G10, a cGAS-STING-specific agonist,... more
Monocyte and DC subsets from older individuals are impaired in TANK-binding kinase (TBK) phosphorylation. Human PBMCs from the blood of younger (age, 24–36 years; n = 11) and older (age, 67–83 years; n = 11) healthy donors were either stimulated with LPS/IFN-γ, G10, a cGAS-STING-specific agonist, or transfected with a RIG-I-specific 3p-hpRNA ligand. a Representative flow plot for data presented in b–d. Using these plots, the fold change of pTBK-1 MFI was calculated using the unstimulated as the control. b–d PBMCs were either stimulated with LPS/IFN-γ, G10, or the RIG-I agonist or left unstimulated for 15 min and 24 h. Cells were permeabilized, fixed, and stained for phosphorylated TBK-1. After gating on DC and monocyte subsets, the MFI was measured using Phosflow cytometry. Data are means. *p < 0.05, **p < 0.01, non-parametric Mann–Whitney U test less

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