Extracellular vesicles in human semen modulate antigen-presenting cell function and decrease downstream antiviral T cell responses

Autoři: Lucia Vojtech aff001;  Mengying Zhang aff002;  Veronica Davé aff003;  Claire Levy aff001;  Sean M. Hughes aff001;  Ruofan Wang aff001;  Fernanda Calienes aff001;  Martin Prlic aff003;  Elizabeth Nance aff002;  Florian Hladik aff001
Působiště autorů: Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America aff001;  Molecular Engineering and Sciences Institute, University of Washington, Seattle, Washington, United States of America aff002;  Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America aff003;  Department of Global Health, University of Washington, Seattle, Washington, United states of America aff004;  Department of Immunology, University of Washington, Seattle, Washington, United States of America aff005;  Department of Chemical Engineering, University of Washington, Seattle, Washington, United States of America aff006;  Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, United States of America aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223901


Human semen contains trillions of extracellular vesicles (SEV) similar in size to sexually transmitted viruses and loaded with potentially bioactive miRNAs, proteins and lipids. SEV were shown to inhibit HIV and Zika virus infectivity, but whether SEV are able also to affect subsequent immune responses is unknown. We found that SEV efficiently bound to and entered antigen-presenting cells (APC) and thus we set out to further dissect the impact of SEV on APC function and the impact on downstream T cell responses. In an APC–T cell co-culture system, SEV exposure to APC alone markedly reduced antigen-specific cytokine production, degranulation and cytotoxicity by antigen-specific memory CD8+ T cells. In contrast, inhibition of CD4+ T cell responses required both APC and T cell exposure to SEV. Surprisingly, SEV did not alter MHC or co-stimulatory receptor expression on APCs, but caused APCs to upregulate indoleamine 2,3 deoxygenase, an enzyme known to indirectly inhibit T cells. Thus, SEV reduce the ability of APCs to activate T cells. We propose here that these immune-inhibitory properties of SEV may be intended to prevent immune responses against semen-derived antigens, but can be hi-jacked by genitally acquired viral infections to compromise adaptive cellular immunity.

Klíčová slova:

Antigen-presenting cells – Cell staining – Cytokines – Cytotoxic T cells – Flow cytometry – Immune response – Semen – T cells


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