Vitamin D treatment of peripheral blood mononuclear cells modulated immune activation and reduced susceptibility to HIV-1 infection of CD4+ T lymphocytes

Autor: Edison Trujillo-Gil, Wbeimar Aguilar-Jimenez, Sandra M. Gonzalez, Wildeman Zapata, María Teresa Rugeles, T. Blake Ball, Ruey-Chyi Su
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
RNA viruses
CD4-Positive T-Lymphocytes
Male
Physiology
Gene Expression
HIV Infections
APOBEC-3G Deaminase
CD38
Pathology and Laboratory Medicine
Lymphocyte Activation
Biochemistry
White Blood Cells
0302 clinical medicine
Immunodeficiency Viruses
Animal Cells
Immune Physiology
Medicine and Health Sciences
Medicine
Cytotoxic T cell
Lipid Hormones
Cells
Cultured
Innate Immune System
Multidisciplinary
biology
T Cells
Virus receptor
Microbial Genetics
Vitamins
Medical Microbiology
Viral Pathogens
Viruses
Cytokines
Viral Genetics
Female
Cellular Types
Pathogens
medicine.drug
Research Article
Interleukin 2
Sexual transmission
Calcitriol
Immune Cells
Science
Immunology
DNA transcription
Primary Cell Culture
Cytotoxic T cells
Peripheral blood mononuclear cell
Microbiology
Immune Activation
03 medical and health sciences
Cathelicidins
Virology
Retroviruses
Genetics
Humans
Microbial Pathogens
Immunity
Mucosal
Blood Cells
business.industry
Lentivirus
Organisms
Immunity
Biology and Life Sciences
HIV
Cell Biology
HLA-DR Antigens
Molecular Development
Hormones
030104 developmental biology
Viral Gene Expression
Granzyme
Immune System
biology.protein
HIV-1
business
030215 immunology
Developmental Biology
Antimicrobial Cationic Peptides
Zdroj: PLoS ONE, Vol 14, Iss 9, p e0222878 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: IntroductionMucosal immune activation, in the context of sexual transmission of HIV-1 infection, is crucial, as the increased presence of activated T cells enhance susceptibility to infection. In this regard, it has been proposed that immunomodulatory compounds capable of modulating immune activation, such as Vitamin D (VitD) may reduce HIV-1 transmission and might be used as a safe and cost-effective strategy for prevention. Considering this, we examined the in vitro effect of the treatment of peripheral blood mononuclear cells (PBMCs) with the active form of VitD, calcitriol, on cellular activation, function and susceptibility of CD4+ T cells to HIV-1 infection.MethodsWe treated PBMCs from healthy HIV unexposed individuals (Co-HC) and frequently exposed, HIV-1 seronegative individuals (HESNs) from Colombia and from healthy non-exposed individuals from Canada (Ca-HC) with calcitriol and performed in vitro HIV-1 infection assays using X4- and R5-tropic HIV-1 strains respectively. In addition, we evaluated the activation and function of T cells and the expression of viral co-receptors, and select antiviral genes following calcitriol treatment.ResultsCalcitriol reduced the frequency of infected CD4+ T cells and the number of viral particles per cell, for both, X4- and R5-tropic viruses tested in the Co-HC and the Ca-HC, respectively, but not in HESNs. Furthermore, in the Co-HC, calcitriol reduced the frequency of polyclonally activated T cells expressing the activation markers HLA-DR and CD38, and those HLA-DR+CD38-, whereas increased the subpopulation HLA-DR-CD38+. Calcitriol treatment also decreased production of granzyme, IL-2 and MIP-1β by T cells and increased the transcriptional expression of the inhibitor of NF-kB and the antiviral genes cathelicidin (CAMP) and APOBEC3G in PBMCs from Co-HC.ConclusionOur in vitro findings suggest that VitD treatment could reduce HIV-1 transmission through a specific modulation of the activation levels and function of T cells, and the production of antiviral factors. In conclusion, VitD remains as an interesting potential strategy to prevent HIV-1 transmission that should be further explored.
Databáze: OpenAIRE
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