BMC Infectious Diseases | |
Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa | |
Gerhard Walzl3  Musawenkosi LH Mabaso1  Zilungile L Mkhize-Kwitshana2  | |
[1] HIV/AIDS, STI and TB, Human Sciences Research Council, Private Bag X07, Dalbridge, Durban 4014, South Africa;School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, P.O. Box 7, Congella 4001, South Africa;Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa | |
关键词: Cytokines; CTLA-4; Ki67; Proliferation; Co-infection; Helminths; HIV; | |
Others : 1125565 DOI : 10.1186/1471-2334-14-499 |
|
received in 2013-12-18, accepted in 2014-09-02, 发布年份 2014 | |
【 摘 要 】
Background
It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa.
Methods
Forty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo).
Results
Individuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production.
Conclusion
The findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.
【 授权许可】
2014 Mkhize-Kwitshana et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150217022312809.pdf | 932KB | download | |
Figure 2. | 109KB | Image | download |
Figure 1. | 70KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Borkow G, Bentwich Z: Chronic immune activation associated with chronic helminthic and human immunodeficiency virus infections: role of hyporesponsiveness and anergy. Clin Microbiol Rev 2004, 17(4):1012-1030.
- [2]Hotez PJ, Mistry N, Rubinstein J, Sachs JD: Integrating neglected tropical diseases into AIDS, tuberculosis, and malaria control. N Engl J Med 2011, 364:2086-2089.
- [3]Lawn SD, Butera S, Folks TM: The contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type1 infection. Clin Microbiol Rev 2001, 14(4):753-777.
- [4]Day CL, Kiepiela P, Leslie AJ, van der Stok M, Nair K, Ismael I, Honeyborne I, Crawford H, Coovadia HM, Goulder PJR, Walker BD, Klenerman P: Proliferative capacity of epitope-specific CD8 T-cell responses is inversely related to viral load in chronic human immunodeficiency virus type 1 infection. J Virol 2007, 81(1):434-438.
- [5]Porto AF, Santos SB, Muniz AL, Basilio V, Rodrigues W Jr, Neva FA, Dutra WO, Gollob KJ, Jacobson S, Carvalho EM: Helminthic infection down-regulates type 1 immune responses in human T cell lymphotropic virus type 1 (HTLV-1) carriers and is more prevalent in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. J Infect Dis 2005, 191(4):612-618.
- [6]Clerici M, Shearer GM: The Th1 -Th2 hypothesis of HIV infection: new insights. Immunol Today 1994, 15(12):575-581.
- [7]Modjarrad K: HIV and helminths: time for a new direction. Lancet Infect Dis 2013, 13(10):835.
- [8]Soares A, Govender A, Hughes J, Mavakla W, deKock M, Barnard C, Pienaar B, Janse van Rensberg E, Jacobs G, Khomba G, Stone L, Abel B, Scriba TJ, Hanekom WA: Novel application of Ki67 to quantify antigen-specific in vitro lymphoproliferation. J Immunol Methods 2010, 362(1–2):43-50. doi:10.1016/j.jim.2010.08.007
- [9]Sachsenberg N, Perelson AS, Yerly S, Schockmel GA, Leduc D, Hirschel B, Perrin L: Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 1998, 187:1295-1303.
- [10]Iatropoulos MJ, Williams GM: Proliferation markers. Exp Toxicol Pathol 1996, 48(2–3):175-181.
- [11]Brunner MC, Chambers CA, Chang FK, Hanke J, Winoto A, Allison JP: CTLA-4 mediated inhibition of early events of T cell proliferation. J Immunol 1999, 15:5813-5820.
- [12]Adams VJ, Markus MB, Kwitshana ZL, Dhansay MA, van der Merwe L, Walzl G, Fincham JE: Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in helminth/HIV co-infection analyses. BMC Infect Dis 2006, 6(88):1-8.
- [13]World Health Organization: World Health Assembly Resolution WHA54. 19: Schistosomiasis and Soil-transmitted Helminth Infections. Geneva: World Health Organization; 2001.
- [14]Mkhize-Kwitshana ZL, Taylor M, Pieter Jooste P, Mabaso MHL, Walzl G: The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa. BMC Infect Dis 2011, 11:273. BioMed Central Full Text
- [15]Ritchie LS: Formol ether concentration. Bulletin of the United States Army Medical Department 1948, 8:326.
- [16]Peters PA, El AM, Warren KS, Mahmoud AA: Quick Kato smear for field quantification of Schistosoma mansoni eggs. AmJTrop Med Hyg 1980, 29:217-219.
- [17]Maizels RM, Yazdanbakhsh M, Allen JE: Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 2003, 3:733-744.
- [18]Leng Q, Borkow G, Weisman Z, Stein M, Kalinkovich A, Bentwich Z: Immune activation correlates better than HIV plasma viral load with CD4 T cell decline during HIV infection. J Acquir Immune Defic Syndr 2001, 27:389-397.
- [19]BD Biosciences. Recommended Assay Procedure: Staining Protocol for Flow Cytometry. [http://www.bdbiosciences.com/external_files/pm/doc/tds/human/live/web_enabled/36521A_556003.pdf webcite] Accessed 22 September 2011
- [20]Grogan JL, Kremsner PG, Deelder AM, Yazdanbakhsh M: Antigen-specific proliferation and interferon-g and interleukin-5 production are down-regulated during Schistosoma haematobium infection. J Infect Dis 1998, 177:1433-7.
- [21]Kalinkovich A, Weisman Z, Greenberg Z, Nahmias J, Eitan S, Stein M, Bentwich Z: Decreased CD4 and increased CD8 counts with T cell activation is associated with chronic helminth infection. Clin Exp Immunol 1998, 114(3):414-421.
- [22]Subramanyam M, Gutheil WG, Bachovchin WW, Huber BT: Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. J Immunol 1993, 150(6):2544-2553.
- [23]Secor WE, Shah A, Mwinzi PMN: Increased density of human immunodeficiency virus type 1 coreceptors CCR5 and CXCR4 on the surfaces of CD4+ T cells and monocytes of patients with Schistosoma mansoni infection. Infect Immun 2003, 71(11):6668-6671.
- [24]Janeway CA, Travers P, Walport M, Shlomchik M: T-Cell Mediated Immunity. In Immunobiology-The immune system in health and Disease. 5th edition. Edited by Schanck D, Austin P, Lawrence E, Gibbs S. USA: Garland Publishing. Taylor and Francis group; 2001:295-340.
- [25]Blish CA, Laura Sangaré LBR, Richardson BA, John-Stewart G, Walson JL: Changes in plasma cytokines following treatment of Ascaris lumbricoides in HIV-1 infected individuals. J Infect Dis 2010, 201(12):1816-1821. doi:10.1086/652784
- [26]Sousa A, Chaves A, Loureiro A, Victorino R: Comparison of the frequency of interleukin2-, interferon –γ-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes. J Infect Dis 2001, 184(5):552-559.
- [27]van Riet E, Hartgers FC, Yazdanbakhsh M: Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 2007, 212:475-490.
- [28]Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD, Allen JE: Helminth parasites- masters of regulation. Immunol Rev 2004, 201:89-116.
- [29]Kocaoemer A, Kerns S, Kluter H, Bieback K: Human AB serum and thrombin-activated platelet –rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells 2007, 25(5):1279-1278.
- [30]BD Biosciences Protocol: Cytokine Flow Cytometry of PBMCs in 96 Well Plates [http://www.bdbiosciences.com webcite]
- [31]Godoy-Ramirez K, Franck K, Mahdavifar S, Andersson L, Gaines H: Optimum culture conditions for specific and nonspecific activation of whole blood and PBMC for intracellular cytokine assessment by flow cytometry. J Immunol Methods 2004, 292:1-15.
- [32]Porichis F, Vlata Z, Hatzidakis G: HIV-1 gp120/V3-derived epitopes promote activation-induced cell death to superantigen–stimulated CD4+/CD45RO+ T cells. Immunol Lett 2007, 108:97-102.