Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging

Kumar, A.; Wang, J.; Zhou, H.; Radcliffe, C.; Vander Wyk, B.; Allore, H.; Tsang, S.; Barakat, L.; Mohanty, S.; Zhao, H.-y.; Shaw, A.; Zapata, H.

doi:10.1101/2022.09.01.505710

bioRxiv · 10.1101/2022.09.01.505710

Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging

Kumar, A.·Wang, J.·Zhou, H.·Radcliffe, C.·Vander Wyk, B.·Allore, H.·Tsang, S.·Barakat, L.·Mohanty, S.·Zhao, H.-y.·Shaw, A.·Zapata, H.

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Abstract

Dectin-1 is an innate immune receptor that recognizes and binds {beta}-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 {beta}-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN- 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- and coagulation response (increased at baseline), a persistent IFN- and IFN-{gamma} 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.

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Kumar, A., Wang, J., Zhou, H., Radcliffe, C., Vander Wyk, B., Allore, H., Tsang, S., Barakat, L., Mohanty, S., Zhao, H.-y., Shaw, A., Zapata, H.. 2022-09-02. Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging. https://doi.org/10.1101/2022.09.01.505710

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