Bryan J. Collazo-Rodríguez, PhD
Natasha N. Alcalá-Molina, BS
Lorivette Ortiz-Valentín, BS
Yisel M. Cantres-Rosario, PhD
Elaine Rodríguez, MT
Janaina Alves, PhD
Valerie Wojna, MD
Yamil Gerena, PhD

Department of Pharmacology and Toxicology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
Department of Microbiology and Medical Zoology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
Neurology Division, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico
Department of Microbiology and Immunology, Universidad Central del Caribe, Bayamón, Puerto Rico

Introduction

Previously, we showed that cytochalasin D (CyD) inhibited the activation of monocytes from HIV-negative women induced by the uptake of plasma exosomes from HIV-positive women stratified by cognitive function. However, both the influence on the activation state and the effects of CyD in noninfected monocytes exposed to exosomes from plasma of virologically suppressed HIV-positive men remain unknown. We hypothesized that uptake of plasma exosomes from antiretroviral therapy (ART)-treated HIV-positive men activates monocytes from HIV-negative men by increasing membrane-bound CD163 or HLA-DR activation markers, and that CyD antagonizes these effects.

Methods

Plasma exosomes from HIV-negative (controls) or HIV-positive women stratified by normal cognition (NC) or symptomatic neurocognitive impairment (SNI) were collected by ultracentrifugation and labeled using PKH-67 fluorescent dye prior to incubation with peripheral blood mononuclear cells (PBMCs) from HIV-negative male donors in the presence or absence of CyD. Monocyte subsets were identified using anti-CD14 and anti-CD16 antibodies, and CD163 or HLA-DR expression was measured using anti-CD163 or anti-HLA-DR antibodies by flow cytometry.

Results

CD163 levels decreased (p = 0.0080) in men’s non-classical monocytes exposed to HIV-positive exosomes, whereas all women’s subpopulations had increased levels. CD163 levels increased significantly in men’s total, intermediate, and non-classical monocytes, and HLA-DR levels increased (p = 0.0317) in intermediate monocytes exposed to SNI exosomes, whereas women’s total monocytes exposed to NC exosomes had higher CD163 levels. Similarly, CD163 percentage and levels decreased significantly in all subpopulations from both men’s and women’s monocytes exposed to HIV-positive exosomes in the presence of CyD, whereas HLA-DR levels decreased significantly in men’s total, classical, and intermediate monocytes.

Conclusion

Our findings support that activation marker expression showed sex-specific changes in monocytes from HIV-negative men and women exposed to HIV-positive exosomes. Further studies are warranted to investigate the role of HIV-induced alterations in sex hormones and the mechanistic differences in immune activation observed between these populations.

IRB Approval Number

1330315

Acknowledgments

This research was supported by R01NS099036, R25GM061838, R21MH095524, and U54MD007600.

Keywords

HIV-positive exosomes, monocyte activation, cytochalasin D, sex differences, cognitive function