ABSTRACT

Background: Proteins of the CD1 family participate in the cellular immune response and present glycolipid antigens to activate antigen specific T lymphocytes. The identification of lipids antigens in the cell wall of Mycobacterium tuberculosis, as well, as the presence of CD1-restricted T lymphocytes in patients with pulmonary tuberculosis; suggests that this system participates actively in the cellular immune response against the bacillus. Our aim in this study was to identify the expression profile of CD1 isoforms in peripheral blood monocytes from pulmonary tuberculosis patients.
Methods: Peripheral blood was obtained from 20 tuberculosis patients and 20 healthy individuals. Mononuclear cells were isolated and incubated with monoclonal antibodies against to CD14, CD1a, CD1b, CD1d and HLA-ABC. Cells were analyzed by flow cytometry.
Results: Tuberculosis patients showed a greater percentage of cells CD14 + (monocytes) expressing CD1b (5, iqr 3-6) when compared with healthy individuals (2, iqr 1-3) (p = 0.0003). Regard to CD1a, CD1d and HLA-ABC expression we did not find statistical significant differences.
Conclusions: Patients with pulmonary tuberculosis have high frequency of CD14+ CD1b+ monocytes, which would be able to activate antigen specific T lymphocytes to induce a more efficient immune response.

KEYWORDS

Tuberculosis, monocytes, CD1a, CD1b, CD1d.

REFERENCES

1. Global tuberculosis control: surveillance, planning, financing: WHO report 2008. WHO/HTM/TB/2008.393.

2. Global tuberculosis control: epidemiology, strategy, financing. WHO report 2009. Accesible en: http://www.who.int/tb/publications/global_report/2009/pdf/key_points_es.pdf

3. Russell DG. Who puts the tubercle in tuberculosis? Nat Rev Microbiol 2007;5:39-47.

4. Bendelac A. CD1: presenting unusual antigens to unusual T lymphocytes. Science 1995;269:185-186.

5. Barral DC, Brenner MB. CD1 antigen presentation: how it works. Nat Rev Immunol 2007;7:929-941.

6. Van Rhijn I, Koets AP, Im JS, et ál. The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d. J Immunol 2006;176:4888-4893.

7. Dascher CC, Hiromatsu K, Xiong X, et ál. Conservation of CD1 intracellular trafficking patterns between mammalian species. J Immunol 2002;169:6951-6958.

8. Bradbury A, Calabi F, Milstein C. Expression of CD1 in the mouse thymus. Eur J Immunol 1990;20:1831-1836.

9. Dougan SK, Kaser A, Blumberg RS. CD1 expression on antigen-presenting cells. Curr Top Microbiol Immunol 2007;314:113-141.

10. Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature 1994;372:691-694.

11. Kinjo Y, Tupin E, Wu D, et ál. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 2006;7:978-986.

12. Naderer T, McConville MJ. The Leishmania-macrophage interaction: a metabolic perspective. Cell Microbiol 2008;10:301-308.

13. Porcelli S, Brenner MB, Greenstein JL, Balk SP, Terhorst C, Bleicher PA. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature 1989;341:447-450.

14. Sada-Ovalle I, Chiba A, Gonzales A, Brenner MB, Behar SM. Innate invariant NKT cells recognize Mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria. PLoS Pathog 2008; 4:e1000239.

15. Tupin E, Kinjo Y, Kronenberg M. The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 2007;5:405-417.

16. Mariotti S, Teloni R, Iona E, et ál. Mycobacterium tuberculosis diverts alpha interferon-induced monocyte differentiation from dendritic cells into immunoprivileged macrophage-like host cells. Infect Immun 2004;72:4385-4392.

17. Rajashree P, Krishnan G, Das SD. Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis. Tuberculosis (Edinb) 2009;89:77-83.

18. Tentori L, Graziani G, Porcelli SA, et ál. Rifampin increases cytokine-induced expression of the CD1b molecule in human peripheral blood monocytes. Antimicrob Agents Chemother 1998;42:550-554.

19. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000;161(4 Pt 1):1376-1395.

20. Brigl M, Brenner MB. CD1: antigen presentation and T cell function. Annu Rev Immunol 2004;22:817-890.

21. Kawashima T, Norose Y, Watanabe Y, et ál. Cutting edge: major CD8 T cell response to live bacillus Calmette-Guérin is mediated by CD1 molecules. J Immunol 2003;170:5345-5348.

22. Rosat JP, Grant EP, Beckman EM, et ál. CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ alpha beta T cell pool. J Immunol 1999;162:366-371.

23. Spada FM, Grant EP, Peters PJ, et ál. Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity. J Exp Med 2000;191:937-948.

24. Stenger S, Mazzaccaro RJ, Uyemura K, et ál. Differential effects of cytolytic T cell subsets on intracellular infection. Science 1997;276:1684-1687.

25. Amprey JL, Späth GF, Porcelli SA. Inhibition of CD1 expression in human dendritic cells during intracellular infection with Leishmania donovani. Infect Immun 2004;72:589-592.

26. Donovan MJ, Jayakumar A, McDowell MA. Inhibition of groups 1 and 2 CD1 molecules on human dendritic cells by Leishmania species. Parasite Immunol 2007;29: 515-524.

27. Mariotti S, Teloni R, Iona E, et ál. Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells. Eur J Immunol 2002; 32:3050-3058.

28. Flynn JL, Chan J. Immune evasion by Mycobacterium tuberculosis: living with the enemy. Curr Opin Immunol 2003;15:450-455.

29. Noss EH, Harding CV, Boom WH. Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages. Cell Immunol 2000;201: 63-74.

30. Hmama Z, Gabathuler R, Jefferies WA, de Jong G, Reiner NE. Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. J Immunol 1998;161:4882-4893.

31. Wojciechowski W, DeSanctis J, Skamene E, Radzioch D. Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette-Guérin involves class II transactivator and depends on the Nramp1 gene. J Immunol 1999;163:2688-2696.

32. Garibay-Escobar A, Estrada-García I, Estrada-Parra S, Santos-Argumedo L. Integrated measurements by flow cytometry of the cytokines IL-2, IFN-gamma, IL-12, TNF-alpha and functional evaluation of their receptors in human blood. J Immunol Methods 2003;280:73-88.

33. Giuliani A, Prete SP, Graziani G, et ál. Influence of Mycobacterium bovis bacillus Calmette Guérin on in vitro induction of CD1 molecules in human adherent mononuclear cells. Infect Immun 2001;69:7461-7470.

34. Roura-Mir C, Wang L, Cheng TY, et ál. Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. J Immunol 2005;175:1758-1766.