Abstract
Pyroptosis cell death in recent thymus emigrants (RTE) CD4+ T lymphocytes plays an important role on HIV-1 infection as a cause of CD4+ T cell depletion, being influenced by several factors, among them, the sex. Thus, the aim of this study was evaluated pyroptosis levels in RTE CD4+ T lymphocytes of individuals under antiretroviral therapy (ART) stratified by sex. Thirty-seven ART-treated HIV-positive patients (22 females and 15 males) and 12 (seven females and five males) clinically health subjects were recruited. Analysis by flow-cytometry of RTE CD4+ cells (CD4+ CD31+ /fluorescent-labeled inhibitors of caspases-Caspase-1+) were performed. Clinical and sociodemographic aspects were also evaluated from medical records. We observed statistically higher levels of pyroptosis RTE CD4+ T cells in male individuals (69.3%) compared with female group (39.1%) (P = 0.0356). Pre- and post-treatment CD4+ T cell counts were also higher in women than men (P = 0.004 and P = 0.012, respectively). Our data provides important evidence of the sex as a potential predictor of immunological reconstitution in ART-treated individuals.
This is a preview of subscription content, log in via an institution to check access.
Change history
24 February 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00251-021-01207-8
References
Abais JM, Xia M, Zhang Y et al (2015) Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? 22:1111–1129. https://doi.org/10.1089/ars.2014.5994
Cai R, Liu L, Luo B et al (2017) Caspase-1 activity in CD4 T cells is downregulated following antiretroviral therapy for HIV-1 infection. AIDS Res Hum Retroviruses 33:164–171. https://doi.org/10.1089/aid.2016.0234
Carvalho-Silva WHV, Andrade-Santos JL, Souto FO et al (2020) Immunological recovery failure in cART-treated HIV-positive patients is associated with reduced thymic output and RTE CD4+ T cell death by pyroptosis. J Leukoc Biol 107:85–94. https://doi.org/10.1002/JLB.4A0919-235R
Castilho JL, Melekhin VV, Sterling TR (2014) Sex differences in HIV outcomes in the highly active antiretroviral therapy era: a systematic review. AIDS Res Hum Retroviruses 5:446–456. https://doi.org/10.1089/aid.2013.0208
Chen FP, Chien MH, Chen HY et al (2013) Effects of estradiol and progestogens on human breast cells: regulation ofsex steroid receptors. Taiwan J Obstet Gynecol 52:365–373. https://doi.org/10.1016/j.tjog.2012.09.038
Chen S, Markman JL, Shimada K et al (2020) Sex-specific effects of the Nlrp3 inflammasome on atherogenesis in LDL receptor-deficient mice. JACC Basic to Transl Sci. https://doi.org/10.1016/j.jacbts.2020.03.016
Corbeau P, Reynes J (2011) Review article Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Therapy 117:5582–5590. https://doi.org/10.1182/blood-2010-12-322453
De Voeght A, Martens H, Renard C et al (2017) Exploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium. PLoS ONE 12:1–11. https://doi.org/10.1371/journal.pone.0185761
Doitsh G, Galloway NLK, Geng X et al (2014) Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505:509–514. https://doi.org/10.1038/nature12940
Doitsh G, Greene WC (2016) Dissecting how CD4 T cells are lost during HIV infection. Cell Host Microbe 19:280–291. https://doi.org/10.1016/j.chom.2016.02.012
Gaardbo JC, Hartling HJ, Gerstoft J, Nielsen SD (2012) Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical care, and possible solutions. Clin Dev Immunol 2012 https://doi.org/10.1155/2012/670957
Galloway NLK, Doitsh G, Monroe KM et al (2015) Cell-to-cell transmission of HIV-1 is required to trigger pyroptotic death of lymphoid-tissue-derived CD4 T cells. Cell Rep 12:1555–1563. https://doi.org/10.1016/j.celrep.2015.08.011
Healthcare, G. E. (2007). Ficoll-Paque Plus intended use for in vitro isolation of lymphocytes. GE Healthcare, Uppsala, Sweden.
Jarrin I, Geskus R, Bhaskaran K et al (2008) Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women. Am J Epidemiol 168:532–540. https://doi.org/10.1093/aje/kwn179
Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638. https://doi.org/10.1038/nri.2016.90
Maskew M, Brennan AT, Westreich D et al (2013) Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients. J Women’s Heal 22:113–120. https://doi.org/10.1089/jwh.2012.3585
Massanella M, Negredo E, Clotet B, Blanco J (2013) Immunodiscordant responses to HAART-mechanisms and consequences. Expert Rev Clin Immunol 9:1135–1149. https://doi.org/10.1586/1744666X.2013.842897
Morrissy S, Xu B, Aguilar D et al (2010) Inhibition of apoptosis by progesterone in cardiomyocytes. Aging Cell 9:799–809. https://doi.org/10.1111/j.1474-9726.2010.00619.x
Pido-Lopez J, Imami N, Aspinall R (2001) Both age and gender affect thymic output: more recent thymic migrants in females than males as they age. Clin Exp Immunol 125:409–413
Qiu T, Ding P, Fu G et al (2017) Immunologic treatment failure among HIV-infected adult patients in Jiangsu province, China. Sci Rep 7:1–6. https://doi.org/10.1038/srep42381
Rodriguez-Galan MC, Bream JH, Farr A, Young HA (2005) Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression. J Immunol 174:2796–2804. https://doi.org/10.4049/jimmunol.174.5.2796
Scully EP (2018) Sex Differences in HIV Infection. Curr HIV/AIDS Rep 15:136–146. https://doi.org/10.1007/s11904-018-0383-2
Straub RH (2007) The complex role of estrogens in inflammation. Endocr Rev 28:521–574. https://doi.org/10.1210/er.2007-0001
VidyaVijayan KK, Karthigeyan KP, Tripathi SP, Hanna LE (2017) Pathophysiology of CD4+ T-cell depletion in HIV-1 and HIV-2 infections. Front Immunol 8:580. https://doi.org/10.3389/fimmu.2017.00580
Yang, X, Su, B, Zhang, X, Liu, Y, Wu, H, Zhang, T (2020) Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders. J Leukoc Biol 107:597–612. https://doi.org/10.1002/JLB.4MR1019-189R
Yang Y, Wang H, Kouadir M et al (2019) Recent advances in the mechanisms of NLRP3 in flammasome activation and its inhibitors. Cell Death Dis. https://doi.org/10.1038/s41419-019-1413-8
Zhang L, Wang Z, Chen Y et al (2015) Label-free proteomic analysis of PBMCs reveals gender differences in response to long-term antiretroviral therapy of HIV. J Proteomics 126:46–53. https://doi.org/10.1016/j.jprot.2015.05.033
Funding
This study was partially supported by grants from CNPq (442225/2014-8), FACEPE (APQ-0599-2.02/14), and CAPES (BEX 7715-15-3) to GUIMARÃES, R. L.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The original online version of this article was revised: The legend that represents Male and Female in the Figure 1b image of the original published version of the above article was cut off. This has been corrected.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Andrade-Santos, J.L., Carvalho-Silva, W.H.V., Souto, F.O. et al. Differences in pyroptosis of recent thymic emigrants CD4+ T Lymphocytes in ART-treated HIV-positive patients are influenced by sex. Immunogenetics 73, 349–353 (2021). https://doi.org/10.1007/s00251-020-01202-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-020-01202-5