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Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.
- Source :
-
Aging [Aging (Albany NY)] 2023 Aug 21; Vol. 15 (16), pp. 7866-7908. Date of Electronic Publication: 2023 Aug 21. - Publication Year :
- 2023
-
Abstract
- Dectin-1 is an innate immune receptor that recognizes and binds β-1, 3/1, 6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with β-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging.
- Subjects :
- Humans
Cytokines
Glucans
Tumor Necrosis Factor-alpha
HIV Infections
Subjects
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 15
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 37606991
- Full Text :
- https://doi.org/10.18632/aging.204927