Changes in the immune status of HIV-infected individuals with chronic toxoplasmosis infestation and toxoplasmosis encephalitis

I.H. Hryzhak

Abstract


Background. Invasion of Toxoplasma gondii in human immunodeficiency virus (HIV) infected persons may cause more profound immunodeficiency, which may contribute to the reactivation of bradyzoites and development of severe opportunistic infections. The aim of our work was to study the features of the immune status of HIV-infected patients, who infested with Toxoplasma and to define the predictors of brain toxoplasmosis. Materials and me­thods. The study involved 61 HIV-positive people (33 individuals seropositive for toxoplasmosis and 28 — seronegative). Enzyme-linked immunosorbent assay was used for determining the titers of specific anti-Toxoplasma gondii immunoglobulin G (IgG) and IgM; total IgM, IgA, IgG, and interleukin-2 (IL-2), IL-4, IL-10, interferon-γ (INF-γ), tumor necrosis factor-2α (TNF-2α). Statistical analysis was performed in statistical software packages Excel using Student’s t-test and Fisher’s z-test, statistical analysis was conducted by Bayes and consistent A. Wald method. Results. In HIV-infected persons, we have identified an imbalance of cytokines compared with healthy individuals. The seronegative for toxoplasmosis patients had elevated levels of IL-4 (1.57 ± 0.30 pg/ml vs. 0.81 ± 0.09 pg/ml, р < 0.001), IL-10 (9.81 ± 0.17 pg/ml vs. 6.70 ± 0.13 pg/ml, р < 0.001), TNF-2α (2.89 ± 0.08 pg/ml vs. 1.90 ± 0.04 pg/ml, р < 0.001), INF-γ (9.30 ± 0.47 pg/ml vs. 4.13 ± 0.12 pg/ml, р < 0.001), and total IgG (20.63 ± 0.65 g/l vs. 16.30 ± 0.94 g/l, р < 0.001). In seropositive individuals, the rates of IL-10 were higher then in seronegative ones (11.88 ± 0.50 pg/ml vs. 9.81 ± 0.17 pg/ml, р < 0.05), as well as INF-γ (10.75 ± 0.44 pg/ml vs. 9.30 ± 0.47 pg/ml, р < 0.05). Combination of 2 features: INF-γ < 8.8 pg/ml and IL-4 < 0.77 pg/ml; or INF-γ < 8.8 pg/ml and IL-10 > 11.8 pg/ml; or 3 signs — IL-4 < 0.77 pg/ml, IL-10 > 11.8 pg/ml and IL-2 < 1.5 pg/ml — is predictive in terms of the development of toxoplasmosis encephalitis. Conclusions. It was found that HIV-positive people have elevated levels of certain pro-inflammatory (TNF-α, INF-γ) and anti-inflammatory (IL-4, IL-10) cytokines, but in people seropositive for toxoplasmosis compared to seronegative ones, the indicators of INF-γ and IL-10 dominated. A manifestation of profound immunopathology and a predictor of toxoplasmosis encephalitis is the reduction of INF-γ, IL-4, IL-2 with increased IL-10 level in seropositive persons.

Keywords


HIV-infection; brain toxoplasmosis; cytokines; immunopathology

References


Hoffmann C, Rockstroh JK, editors. HIV 2015/16. Available from: https://hivbook.com. Accessed: February 11, 2017.

Miedema F, Hazenberg MD, Tesselaar K, van Baarle D, de Boer RJ, Borghans JA. Immune Activation and Collateral Damage in AIDS Pathogenesis. Front Immunol. 2013;4:298. doi: https://doi.org/10.3389/fimmu.2013.00298.

Zaporozhan VM, Aryayev ML, compilers. VIL-infektsiya i SNID [HIV-infection and AIDS]. 2nd ed., rev. and suppl. Kiev: Zdorov’ya; 2004. 636 p. (in Ukrainian).

Aaronson DS, Horvath CM. A road map for those who don’t know JAK-STAT. Science. 2002 May;296(5573):1653-5. doi:10.1126/science.1071545. PMID: 12040185.

Kim SK, Fouts AE, Boothroyd JC. Toxoplasma gondii dysre­gulates IFN-gamma-inducible gene expression in human fibroblasts: insights from a genome-wide transcriptional profiling. J Immunol. 2007;178(8):5154-65. PMID: 17404298.

Lang C, Algner M, Beinert N, Gross U, Luder CG. Diverse mechanisms employed by Toxoplasma gondii to inhibit IFN-gamma-induced major histocompatibility complex class II gene expression. Microbes Infect. 2006;8(8):1994-2005. PMID: 16824778. doi: http://dx.doi.org/10.1016/j.micinf.2006.02.031.

Luder CG, Walter W, Beuerle B, Maeurer MJ, Gross U. Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1alpha. Eur J Immunol. 2001;31(5):1475-84. PMID: 11465104.

Adams LB, Hibbs JBJr, Taintor RR, Krahenbuhl JL. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. Journal of immunology. 1990;144(7):2725-2729.

Jun CD, Kim SH, Soh CT, Kang SS, Chung HT. Nitric oxide mediates the toxoplasmastatic activity of murine microglial cells in vitro. Immunol Invest. 1993;22(8):487-501. doi: http://dx.doi.org/10.3109/08820139309084178.

Chao CC, Anderson WR, Hu S, Gekker G, Martella A, Peterson PK. Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism. Clin Immunol Immunopathol. 1993;67(2):178-183. doi: http://dx.doi.org/10.1006/clin.1993.1062.

Koide M, Kawahara Y, Tsuda T, Yokoyama M. Cytokine-induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cells. FEBS Lett. 1993;318(3):213-217. doi: 10.1016/0014-5793(93)80514-U.

Zhao Y, Ferguson DJ, Wilson DC, Howard JC, Sibley LD, Yap GS. Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages. Journal of immunology. 2009;182(6):3775-3781. doi: 10.4049/jimmunol.0804190.

Langermans JA, Hulst Vander ME, Nibbering PH, Hiemstra PS, Fransen L, Van Furth R. IFN-gamma-induced L-arginine-dependent toxoplasmastatic activity in murine peritoneal macrophaes is mediated by endogenous tumor necrosis factor-alpha. Journal of immunology. 1992;148(2):568-574. PMID: 1729374.

Jana M, Liu X, Koka S, Ghosh S, Petro TM, Pahan K. Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglialcells. J Biol Chem. 2001;276(48):44527-44533. doi: 10.1074/jbc.M106771200.

Drannyk HN, editor. Klinichna imunolohiia i alerholohiia [Clinical immonology and allergology]. Kiev: Polyhraf plius; 2006. 482 p. (in Ukrainian).

Khan IA, Matsuura T, Kasper LH. IL-10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice. Parasite immunology. 1995;17(4):185-195. doi: 10.1111/j.1365-3024.1995.tb00888.x.

Glantz S, compilar. Mediko-biologicheskaya statistika [Biomedical statistics]. 4th ed. Moscow: Praktika; 1999. 459p. (in Russian).

Toxoplasmosis (Toxoplasma Infection). Center for Disease Control and Prevention (US): Resources for Health Professionals. Available from: http://www.cdc.gov/parasites/toxoplasmosis/health_professionals/index.html#tx. Accessed: February 11, 2017.

Clinical protocol for diagnosis and treatment of opportunistic infections and general symptoms in HIV-infected adults and adolescents. Available from: http://ucdc.gov.ua/uploads/documents/5416f7/5e383386d320c87999c2801c80fcdcd8.pdf.




DOI: https://doi.org/10.22141/2312-413x.5.1.2017.98771

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