Vitamin D treatment of peripheral blood mononuclear cells modulated immune activation and reduced susceptibility to HIV-1 infection of CD4+ T lymphocytes
Autoři:
Sandra M. Gonzalez aff001; Wbeimar Aguilar-Jimenez aff001; Edison Trujillo-Gil aff001; Wildeman Zapata aff001; Ruey-Chyi Su aff002; T. Blake Ball aff002; Maria T. Rugeles aff001
Působiště autorů:
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia
aff001; National HIV and Retrovirology Laboratory, JC Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
aff002; Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia
aff003; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada
aff004
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222878
Souhrn
Introduction
Mucosal 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.
Methods
We 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.
Results
Calcitriol 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.
Conclusion
Our 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.
Klíčová slova:
Cytokines – T cells – Cytotoxic T cells – HIV-1 – DNA transcription – Calcitriol – Immune activation – Viral gene expression
Zdroje
1. Shapira-Nahor O, Kalinkovich A, Weisman Z, Greenberg Z, Nahmias J, Shapiro M, et al. Increased susceptibility to HIV-1 infection of peripheral blood mononuclear cells from chronically immune-activated individuals. AIDS. 1998;12(13):1731–3. 9764802
2. Zhang Z, Schuler T, Zupancic M, Wietgrefe S, Staskus KA, Reimann KA, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science. 1999;286(5443):1353–7. doi: 10.1126/science.286.5443.1353 10558989
3. Lawn SD, Butera ST, Folks TM. Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection. Clin Microbiol Rev. 2001;14(4):753–77. doi: 10.1128/CMR.14.4.753-777.2001 11585784
4. Aguilar-Jimenez W, Villegas-Ospina S, Gonzalez S, Zapata W, Saulle I, Garziano M, et al. Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro. JAIDS J Acquir Immune Defic Syndr. 2016;73(5):497–506. doi: 10.1097/QAI.0000000000001150 27509245
5. Meditz AL, Haas MK, Folkvord JM, Melander K, Young R, McCarter M, et al. HLA-DR+ CD38+ CD4+ T Lymphocytes Have Elevated CCR5 Expression and Produce the Majority of R5-Tropic HIV-1 RNA In Vivo. J Virol. 2011;85(19):10189–200. doi: 10.1128/JVI.02529-10 21813616
6. Card CM, Ball T, Fowke KR. Immune Quiescence: a model of protection against HIV infection. Retrovirology. 2013;10(1):141.
7. Card CM, McLaren PJ, Wachihi C, Kimani J, Plummer FA, Fowke KR. Decreased Immune Activation in Resistance to HIV-1 Infection Is Associated with an Elevated Frequency of CD4 + CD25 + FOXP3 + Regulatory T Cells. J Infect Dis. 2009;199(9):1318–22. doi: 10.1086/597801 19301980
8. McLaren PJ, Ball TB, Wachihi C, Jaoko W, Kelvin DJ, Danesh A, et al. HIV-Exposed Seronegative Commercial Sex Workers Show a Quiescent Phenotype in the CD4 + T Cell Compartment and Reduced Expression of HIV-Dependent Host Factors. J Infect Dis. 2010;202(S3):S339–44.
9. Koning FA, Otto SA, Hazenberg MD, Dekker L, Prins M, Miedema F, et al. Low-level CD4+ T cell activation is associated with low susceptibility to HIV-1 infection. J Immunol. 2005;175(9):6117–22. doi: 10.4049/jimmunol.175.9.6117 16237108
10. Kuebler PJ, Mehrotra ML, Shaw BI, Leadabrand KS, Milush JM, York VA, et al. Persistent HIV Type 1 Seronegative Status Is Associated With Lower CD8+ T-Cell Activation. J Infect Dis. 2016;213(4):569–73. doi: 10.1093/infdis/jiv425 26310308
11. Chege D, Chai Y, Huibner S, Kain T, Wachihi C, Kimani M, et al. Blunted IL17/IL22 and Pro-Inflammatory Cytokine Responses in the Genital Tract and Blood of HIV-Exposed, Seronegative Female Sex Workers in Kenya. PLoS One. 2012;7(8):e43670. doi: 10.1371/journal.pone.0043670 22928014
12. Lajoie J, Juno J, Burgener A, Rahman S, Mogk K, Wachihi C, et al. A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers. Mucosal Immunol. 2012;5(3):277–87. doi: 10.1038/mi.2012.7 22318497
13. Fulcher JA, Romas L, Hoffman JC, Elliott J, Saunders T, Burgener AD, et al. Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal Innate Immune Reactivity. AIDS Res Hum Retroviruses. 2017;33(8):788–95. doi: 10.1089/AID.2017.0014 28503933
14. Lin R, White JH. The pleiotropic actions of vitamin D. BioEssays. 2004;26(1):21–8. doi: 10.1002/bies.10368 14696037
15. Wang T-T, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909–12. doi: 10.4049/jimmunol.173.5.2909 15322146
16. Penna G, Adorini L. 1,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation. J Immunol. 2000;164(5):2405–11. doi: 10.4049/jimmunol.164.5.2405 10679076
17. Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A. Vitamin D decreases NFκB activity by increasing IκBα levels. Nephrol Dial Transplant. 2006;21(4):889–97. doi: 10.1093/ndt/gfi254 16455676
18. Aguilar-Jiménez W, Zapata W, Caruz A, Rugeles MT. High Transcript Levels of Vitamin D Receptor Are Correlated with Higher mRNA Expression of Human Beta Defensins and IL-10 in Mucosa of HIV-1-Exposed Seronegative Individuals. PLoS One. 2013 Jan;8(12):e82717. doi: 10.1371/journal.pone.0082717 24349345
19. Aguilar-Jimenez W, Zapata W, Rugeles MT. Antiviral molecules correlate with vitamin D pathway genes and are associated with natural resistance to HIV-1 infection. Microbes Infect. 2016;18(7–8):510–6. doi: 10.1016/j.micinf.2016.03.015 27083474
20. Villegas-Ospina S, Aguilar-Jimenez W, Gonzalez SM, Rugeles MT. Vitamin D modulates the expression of HLA-DR and CD38 after in vitro activation of T-cells. Horm Mol Biol Clin Investig. 2017;29(3):93–103. doi: 10.1515/hmbci-2016-0037 28222027
21. Hewison M, Freeman L, Hughes S V., Evans KN, Bland R, Eliopoulos AG, et al. Differential Regulation of Vitamin D Receptor and Its Ligand in Human Monocyte-Derived Dendritic Cells. J Immunol. 2003;170(11):5382–90. doi: 10.4049/jimmunol.170.11.5382 12759412
22. O’Doherty U, Swiggard WJ, Malim MH. Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol. 2000;74(21):10074–80. doi: 10.1128/jvi.74.21.10074-10080.2000 11024136
23. Coussens AK, Naude CE, Goliath R, Chaplin G, Wilkinson RJ, Jablonski NG. High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans. Proc Natl Acad Sci U S A. 2015;112(26):8052–7. doi: 10.1073/pnas.1500909112 26080414
24. Biswas P, Mengozzi M, Mantelli B, Delfanti F, Brambilla A, Vicenzi E, et al. 1,25-Dihydroxyvitamin D3 upregulates functional CXCR4 human immunodeficiency virus type 1 coreceptors in U937 minus clones: NF-kappaB-independent enhancement of viral replication. J Virol. 1998;72(10):8380–3. 9733889
25. Pauza CD, Kornbluth R, Emau P, Richman DD, Deftos LJ. Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages. J Leukoc Biol. 1993;53(2):157–64. doi: 10.1002/jlb.53.2.157 8383166
26. Locardi C, Petrini C, Boccoli G, Testa U, Dieffenbach C, Buttò S, et al. Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production. J Virol. 1990;64(12):5874–82. 1700829
27. Kuebler PJ, Mehrotra ML, Shaw BI, Leadabrand KS, Milush JM, York VA, et al. Persistent HIV Type 1 Seronegative Status Is Associated With Lower CD8 + T-Cell Activation. J Infect Dis. 2016;213(4):569–73. doi: 10.1093/infdis/jiv425 26310308
28. Savarino A, Bottarel F, Calosso L, Feito MJ, Bensi T, Bragardo M, et al. Effects of the human CD38 glycoprotein on the early stages of the HIV-1 replication cycle. FASEB J. 1999;13(15):2265–76. doi: 10.1096/fasebj.13.15.2265 10593874
29. Sandoval-Montes C, Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T cells with reduced proliferation but improved potential to produce cytokines. J Leukoc Biol. 2005;77(4):513–21. doi: 10.1189/jlb.0404262 15618297
30. Savarino A, Bensi T, Chiocchetti A, Bottarel F, MesturinI R, Ferrero E, et al. Human CD38 interferes with HIV-1 fusion through a sequence homologous to the V3 loop of the viral envelope glycoprotein gp120. FASEB J. 2003;17(3):461–3. doi: 10.1096/fj.02-0512fje 12551845
31. Bensi T, Mele F, Ferretti M, Norelli S, El Daker S, Chiocchetti A, et al. Evaluation of the antiretroviral effects of a PEG-conjugated peptide derived from human CD38. Expert Opin Ther Targets. 2009;13(2):141–52. doi: 10.1517/14728220802637147 19236233
32. Vidyarani M, Selvaraj P, Raghavan S, Narayanan PR. Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis. Exp Mol Pathol. 2009;86(1):69–73. doi: 10.1016/j.yexmp.2008.10.002 19014932
33. Sarkar S, Hewison M, Studzinski GP, Li YC, Kalia V. Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer. Crit Rev Clin Lab Sci. 2016;53(2):132–45. doi: 10.3109/10408363.2015.1094443 26479950
34. Matilainen JM, Räsänen A, Gynther P, Väisänen S. The genes encoding cytokines IL-2, IL-10 and IL-12B are primary 1α,25(OH)2D3 target genes. J Steroid Biochem Mol Biol. 2010;121(1–2):142–5. doi: 10.1016/j.jsbmb.2010.03.020 20236616
35. Ragab D, Soliman D, Samaha D, Yassin A. Vitamin D status and its modulatory effect on interferon gamma and interleukin-10 production by peripheral blood mononuclear cells in culture. Cytokine. 2016;85:5–10. doi: 10.1016/j.cyto.2016.05.024 27269178
36. Giulietti A, van Etten E, Overbergh L, Stoffels K, Bouillon R, Mathieu C. Monocytes from type 2 diabetic patients have a pro-inflammatory profile. Diabetes Res Clin Pract. 2007;77(1):47–57. doi: 10.1016/j.diabres.2006.10.007 17112620
37. Neve A, Corrado A, Cantatore FP. Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin Exp Med. 2014;14(3):275–83. doi: 10.1007/s10238-013-0249-2 23824148
38. Khoo A-L, Chai LYA, Koenen HJPM, Sweep FCGJ, Joosten I, Netea MG, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol. 2011;164(1):72–9. doi: 10.1111/j.1365-2249.2010.04315.x 21323660
39. Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW. Vitamin D Decreases Respiratory Syncytial Virus Induction of NF- B-Linked Chemokines and Cytokines in Airway Epithelium While Maintaining the Antiviral State. J Immunol. 2010;184(2):965–74. doi: 10.4049/jimmunol.0902840 20008294
40. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008;181(10):7090–9. doi: 10.4049/jimmunol.181.10.7090 18981129
41. Lachmann R, Bevan MA, Kim S, Patel N, Hawrylowicz C, Vyakarnam A, et al. A comparative phase 1 clinical trial to identify anti-infective mechanisms of vitamin D in people with HIV infection. AIDS. 2015;29(10):1127–35. doi: 10.1097/QAD.0000000000000666 25870995
42. Wu-Wong JR, Nakane M, Chen Y, Qiang W. Different Effects of Calcidiol and Calcitriol on Regulating Vitamin D Receptor Target Gene Expression in Human Vascular Smooth Muscle Cells. Journal of cardiovascular disease research. 2013;1(2):15–20.
43. Szabo G, Mandrekar P, Girouard L, Catalano D. Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production. Alcohol Clin Exp Res. 1996;20(5):900–7. doi: 10.1111/j.1530-0277.1996.tb05269.x 8865966
44. Mandrekar P, Catalano D, White B, Szabo G. Moderate alcohol intake in humans attenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Alcohol Clin Exp Res. 2006;30(1):135–9. doi: 10.1111/j.1530-0277.2006.00012.x 16433741
45. Barr T, Helms C, Grant K, Messaoudi I. Opposing Effects of Alcohol on the Immune System. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65: 242–251. doi: 10.1016/j.pnpbp.2015.09.001 26375241
Článok vyšiel v časopise
PLOS One
2019 Číslo 9
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Je Fuchsova endotelová dystrofie rohovky neurodegenerativní onemocnění?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania