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Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration.

ABSTRACT: Semen exosomes (SE) from HIV-uninfected (HIV-) individuals potently inhibit HIV infection in vitro. However, morphological changes in target cells in response to SE have not been characterized or have the effect of HIV infection or the use of illicit substances, specifically psychostimulants, on the function of SE been elucidated. The objective of this study was to evaluate the effect of HIV infection, psychostimulant use, and both together on SE-mediated regulation of monocyte function. SE were isolated from semen of HIV- and HIV-infected (HIV+) antiretroviral therapy (ART)-naive participants who reported either using or not using psychostimulants. The SE samples were thus designated as HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+. U937 monocytes were treated with different SEs and analyzed for changes in transcriptome, morphometrics, actin reorganization, adhesion, and chemotaxis. HIV infection and/or use of psychostimulants had minimal effects on the physical characteristics of SE. However, different SEs had diverse effects on the messenger RNA signature of monocytes and rapidly induced monocyte adhesion and spreading. SE from HIV infected or psychostimulants users but not HIV-Drug- SE, stimulated actin reorganization, leading to the formation of filopodia-like structures and membrane ruffles containing F-actin and vinculin that in some cases were colocalized. All SE stimulated monocyte chemotaxis to HIV secretome and activated the secretion of matrix metalloproteinases, a phenotype exacerbated by HIV infection and psychostimulant use. SE-directed regulation of cellular morphometrics and chemotaxis depended on the donor clinical status because HIV infection and psychostimulant use altered SE function. Although our inclusion criteria specified the use of cocaine, humans are poly-drug and alcohol users and our study participants used psychostimulants, marijuana, opiates, and alcohol. Thus, it is possible that the effects observed in this study may be due to one of these other substances or due to an interaction between different substances.

SUBMITTER: Lyu Y

PROVIDER: S-EPMC6770851 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration.

Lyu Yuan Y Kaddour Hussein H Kopcho Steven S Panzner Tyler D TD Shouman Nadia N Kim Eun-Young EY Martinson Jeremy J McKay Heather H Martinez-Maza Otoniel O Margolick Joseph B JB Stapleton Jack T JT Okeoma Chioma M CM

Cells 20190903 9

Semen exosomes (SE) from HIV-uninfected (HIV-) individuals potently inhibit HIV infection in vitro. However, morphological changes in target cells in response to SE have not been characterized or have the effect of HIV infection or the use of illicit substances, specifically psychostimulants, on the function of SE been elucidated. The objective of this study was to evaluate the effect of HIV infection, psychostimulant use, and both together on SE-mediated regulation of monocyte function. SE were ...[more]

PMID: 31484431

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Project description:BackgroundMonocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA.Hypothesis/objectivesThat OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses.AnimalsEighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controlsMethodsClinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs.ResultsCell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018).Conclusions and clinical importanceDogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA.

Project description:BACKGROUND:Epidemiological evidence remains equivocal on the associations between environmentally relevant levels of per-/polyfluoroalkyl substances (PFASs) and human semen quality. OBJECTIVES:We aimed to test whether the potential effects on semen quality could be better observed when seminal PFAS levels were used as an exposure marker compared with serum PFAS levels. METHODS:Matched semen and serum samples from 664 adult men were collected from a cross-sectional population in China from 2015 to 2016. Multiple semen parameters were assessed, along with measurement of 16 target PFASs in semen and serum. Partitioning between semen and serum was evaluated by the ratio of matrix-specific PFAS concentrations. Regression model results were expressed as the difference in each semen parameter associated with the per unit increase in the ln-transformed PFAS level after adjusting for confounders. RESULTS:Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and emerging chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were detected at their highest concentrations in both semen and serum, with median concentrations of 0.23, 0.10, and 0.06?ng/mL in semen, respectively, and a semen-to-serum ratio of 1.3:3.1. The between-matrix correlations of these PFAS concentrations were high (R=0.70-0.83). Seminal PFOA, PFOS, and 6:2 Cl-PFESA levels were significantly associated with a lower percentage of progressive sperm and higher percentage of DNA fragmentation (false discovery rate-adjusted p-values?of<0.05). Associations between serum PFAS levels and semen parameters were generally statistically weaker, except for DNA stainability, which was more strongly associated with serum-based PFASs than with semen-based PFASs. CONCLUSIONS:Our results suggest the potential for deleterious effects following exposure to 6:2 Cl-PFESA and other PFASs. Compared with serum PFAS levels, the much clearer association of seminal PFAS levels with semen parameters suggests its advantage in hazard assessment on semen quality, although the potential for confounding might be higher. Exposure measurements in target tissue may be critical in clarifying effects related to PFAS exposure. https://doi.org/10.1289/EHP4431.

Dataset Information

Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration.

Publications

Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration.

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