Heterogeneity of NK-cells in pulmonary tuberculous granulomas, including association with HIV infection

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Abstract

Interest in the study of cell population heterogeneity among immune system grows with advances in multicolor flow cytometry techniques. Natural killer cells are represented by several subpopulations. Their maturation is a continuous process that begins with CD27-CD11b--cells and ends with mature cells with the CD27-CD11b+-phenotype. Phthisiology is one of the areas for studying the NK-cell polymorphism due to the fact that the mechanism of prolonged persistence of M. tuberculosis in the human body is not fully understood. Moreover, there is increasing number of patients with infectious comorbidities, including the human immunodeficiency virus (HIV) infection. The aim of this study was to determine some subpopulations of NK cells in the patients with pulmonary tuberculous granuloma, as well as in the absence of a synergistic HIV infection.
The study involved 46 people grouped in three cohorts. The 1st group included 24 practically healthy people, the 2nd group consisted of 12 patients with pulmonary tuberculous granuloma without clinical and laboratory signs of HIV infection, and the 3rd group was represented by 10 patients with pulmonary tuberculous granuloma infected with HIV. The causative agent of pulmonary tuberculosis in all patients was drug-resistant. All the patients with HIV infection had stage 4 disease. Immunological status was assessed by flow cytometry. The following cell populations were detected: CD45+CD3+CD19-, CD45+CD3-CD19+, CD45+CD3-CD16+CD56+, CD3+CD16+CD56+, CD45+CD3-CD8+, CD45+CD3-HLA-DR+, CD45+CD3-CD16+CD56+CD11b+. Leukocytosis and leukogram were determined with a 5 Diff Mythic 22 AL clinical analyzer (Cormay, Poland). Statistical studies of the data were performed in the Windows 10 operating environment (Microsoft Corp., USA); the computer program Statistica v. 12.5 (StatSoft, USA) was used. The normality of the data distribution was also evaluated. Kruskal–Wallis one-way analysis of variance (pk-w) was used as criterion for assessing differences between the compared groups at a significance level of differences p < 0.017 (between three unrelated groups), as well as Wald–Wolfowitz test (pw-w) with a significance level of differences p < 0.05. Factor analysis was performed.
We have found that the presence of pulmonary tuberculous granuloma is accompanied by a decrease of NK-cells number by 33%, a two-fold decrease in the number of NKT-cells, a 34.3% decrease in the population of CD3-HLA-DR+-cells, and a 21.7% decrease in the number of CD3-CD16+CD56+CD11b+-cells. Coinfection with HIV in cases of pulmonary tuberculous granuloma was associated with a three-fold decrease in the leukocyte numbers, significant variability in lymphocyte counts, e.g., 3-fold decrease in NK-cell counts, with NK-cells expressing α-chain of the CD8 antigen decreased by 2.3 times; 6-fold drop of NKT-cell, CD3-HLA-DR+-cells decreased by 42.9%; 2.3-fold decline in CD3-CD16+CD56+CD11b+-cells. Decreased control of M. tuberculosis infection was observed both in patients with pulmonary tuberculous granuloma, and in presence of HIV infection as associated comorbidity.

About the authors

O. V. Berdyugina

Institute of Immunology and Physiology, Ural Branch

Author for correspondence.
Email: berolga73@rambler.ru
ORCID iD: 0000-0003-3479-9730

PhD, MD (Biology), Leading Research Associate, Laboratory of Inflammation Immunology

620049, Ekaterinburg, Pervomayskaya str., 106

Russian Federation

References

  1. Addison E.G., North J., Bakhsh I., Marden C., Haq S., Al-Sarraj S., Malayeri R., Wickremasinghe R.G., Davies J.K., Lowdell M.W. Ligation of CD8alpha on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity. Immunology, 2005, Vol. 116, pp. 354-361.
  2. Ahmad F., Hong H.S., Jäckel M., Jablonka A., Lu I.N., Bhatnagar N., Eberhard J.M., Bollmann B.A., Ballmaier M., Zielinska-Skowronek M., Schmidt R.E., Meyer-Olson D. High frequencies of polyfunctional CD8+ NK Cells in Chronic HIV-1 infection are associated with slower disease progression. J. Virol., 2014, Vol. 88, no. 21, pp. 12397-12408.
  3. Barcelos W., Sathler-Avelar R., Martins-Filho O.A., Carvalho B.N., Guimarães T.M., Miranda S.S., Andrade H.M., Oliveira M.H., Toledo V.P. Natural killer cell subpopulations in putative resistant individuals and patients with active Mycobacterium tuberculosis infection. Scand. J. Immunol., 2008, Vol. 68, pp. 92-102.
  4. Baumgarth N., Roederer M. A practical approach to multicolor flow cytometry for immunophenotyping. J. Immunol. Methods, 2000, Vol. 243, no. 1-2, pp. 77-97.
  5. Chiossone L., Chaix J., Fuseri N., Roth C., Vivier E., Walzer T. Maturation of mouse NK cells is a 4-stage developmental program. Blood, 2009, Vol. 113, no. 22, pp. 5488-5496.
  6. Flores-Montero J., Kalina T., Corral-Mateos A., Sanoja-Flores L., Pérez-Andrés M., Martin-Ayuso M., Sedek L., Rejlova K., Mayado A., Fernández P., van der Velden V., Bottcher S., van Dongen J.J.M., Orfao A. Fluorochrome choices for multi-color flow cytometry. J. Immunol. Methods, 2019, Vol. 475, 112618. doi: 10.1016/j.jim.2019.06.009.
  7. Fu B., Tian Z., Wei H. Subsets of human natural killer cells and their regulatory effects. Immunology, 2014, Vol. 141, no. 4, pp. 483-489.
  8. Fu B., Wang F., Sun R., Ling B., Tian Z., Wei H CD11b and CD27 reflect distinct population and functional specialization in human natural killer cells. Immunology, 2011, Vol. 133, no. 3, pp. 350-359.
  9. Goh W., Huntington N.D. Regulation of murine natural killer cell development. Front. Immunol., 2017, Vol. 8, 130. doi: 10.3389/fimmu.2017.00130.
  10. Harris L.D., Khayumbi J., Ongalo J., Sasser L.E., Tonui J., Campbell A., Odhiambo F.H., Ouma S.G., Alter G., Gandhi N.R., Day C.L. Distinct human NK cell phenotypes and functional responses to Mycobacterium tuberculosis in adults from TB endemic and non-endemic regions. Front. Cell. Infect. Microbiol., 2020, Vol. 10, 120. doi: 10.3389/fcimb.2020.00120.
  11. Isvoranu G., Surcel M., Huică R., Munteanu A.N., Pîrvu I.R., Ciotaru D., Constantin C., Bratu O., Neagu M., Ursaciuc C. Natural killer cell monitoring in cutaneous melanoma - new dynamic biomarker. Oncol. Lett., 2019, Vol. 17, no. 5, pp. 4197-4206.
  12. Milush J.M., López-Vergès S., York V.A., Deeks S.G., Martin J.N., Hecht F.M., Lanier L.L., Nixon D.F. CD56 neg CD16 + NK cells are activated mature NK cells with impaired effector function during HIV-1 infection. Retrovirology, 2013, Vol. 10, 158. doi: 10.1186/1742-4690-10-158.
  13. Pohlmeyer C.W., Gonzalez V.D., Irrinki A., Ramirez R.N., Li L., Mulato A., Murry J.P., Arvey A., Hoh R., Deeks S.G., Kukolj G., Cihlar T., Pflanz S., Nolan G.P., Min-Oo G. Identification of NK cell subpopulations that differentiate HIV-infected subject cohorts with diverse levels of virus control. J. Virol., 2019, Vol. 93, no. 7, e01790-18.
  14. Poli A., Michel T., Thérésine M., Andrès E., Hentges F., Zimmer J. CD56bright natural killer (NK) cells: an important NK cell subset. Immunology, 2009, Vol. 126, no. 4, pp. 458-465.
  15. Venkatasubramanian S., Cheekatla S., Paidipally P., Tripathi D., Welch E., Tvinnereim A. R., Nurieva R., Vankayalapati R. IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis. Mucosal Immunol., 2017, Vol. 10, pp. 1031-1042.
  16. Zimmer J. CD56dimCD16dim Natural Killer (NK) cells: the forgotten population. Hemasphere, 2020, Vol. 4, no. 2, e348. doi: 10.1097/HS9.0000000000000348.

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Copyright (c) 2021 Berdyugina O.V.

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Свидетельство о регистрации СМИ ПИ № 77 - 11525 от 04.01.2002 выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


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