FUNCTIONAL AND METABOLIC FEATURES OF BLOOD PHAGOCYTES AT DIFFERENT FORMS OF TUBERCULAR INFLAMMATORY PROCESS OF LUNGS

A leading role of phagocytes in prevention of M. tuberculosis infection is well established. Various clinical variants of tubercular inflammatory process necessitate further studies of functional and metabolic features of blood phagocytes in the patients with different forms of lung tuberculosis, being the main goal of this study. We have observed a total of 124 persons including 25 healthy subjects, and 99 patients with tuberculosis who manifested with different types of tubercular inflammatory process, i.e., 31 patients had a limited specific process (tuberculoma); in 44 patients, an infiltrative lung tuberculosis was diagnosed, and 24 patients had fibro-cavernous tuberculosis of lungs. We studied activation markers of neutrophils and monocytes (phagotest, burst-test, CD11b+, CD11c+, HLA-DR-Ag), as well as main indicators of cellular immunity (CD45+CD3+, CD45+CD19+, CD45+CD3- CD16+56+). Statistical evaluation was carried out in the «Microsoft Office Excel 2007» and «Statistica for Windows v. 6.1» environment.

A considerable decrease in proportion of superoxide anion-producing monocytes was found in 10% of the patients with fibro-cavernous tuberculosis as compared to the patients with tuberculoma and infiltrative tuberculosis. Similarly, the fibro-cavernous tuberculosis was characterized by higher expression of adhesion markers, e.g., CD11b, by 49%, and CD11c, by 73.5%, when compared with the two other groups of patients. A considerable decrease of absorbing granulocyte function was found in the patients with active forms of tuberculosis, as compared with limited clinical forms (tuberculoma). Fibro-cavernous tuberculosis was associated with increased absolute numbers of granulocyte that produce both superoxide anion, and express surface CD11b+ and CD11c+. We have revealed a relative decrease in lymphocyte quantities in the patients from tuberculoma which corresponded to increased granulocyte quantities of granulocytes and monocytes in the patients’ blood. The conducted study allowed us to make a conclusion that each clinical form of tuberculosis id characterized by a specific immunological pattern.

In the patients with tuberculoma, we have revealed a decrease of phagocytic, functional and metabolic activities of monocytes is noted, along with increased quantities of CD11b+ and CD11c+ adhesion molecules on granulocytes, increased numbers of T-lymphocytes, and decreased amounts of NK-cells. Infiltrative tuberculosis is characterized by increased contents and higher HLA-DR expression of the monocytes, with enhanced expression of CD11b+ and CD11c+ adhesion molecules on the granulocytes, and decreased number of T-lymphocytes. In the fibro-cavernous tuberculosis we observed leukocytosis, monocytosis, granulocytosis. The main functional feature of this clinical form is an increased amount of CD 11b+ and CD 11с+-bearing leukocytes, higher functional and metabolic activity of granulocytes, as well as expansion of CD11b+ expressing cell population and increased numbers of B-cells in peripheral blood.

1. Мордык А.В., Батищева Т.Л., Брюханова Н.С., Пузырева Л.В. Влияние иммунологических нарушений на исход впервые выявленного инфильтративного туберкулеза у социально сохранных пациентов // Инфекция и иммунитет, 2014. Т. 4, №4. С. 353-358.[Mordyk A.V., Batishcheva T.L., Bryukhanova N.S., Puzyreva L.V. Influence of immunological disorders on an outcome for the first time diadnosed infiltrative tuberculosis in socially safe patients. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2014, Vol. 4, no. 4, pp. 353-358. doi: 10.15789/2220-7619-2014-4-353-358 (In Russ.)]

2. Ameglio F., Casarini M., Capoluongo E., Mattia P., Puglisi G., Giosuè S. Post-treatment changes of six cytokines in active pulmonary tuberculosis: differences between patients with stable or increased fibrosis. Int. J. Tuberc. Lung. Dis., 2005, Vol. 9, no. 1, pp. 98-104.

3. Ariga H., Harada N. Evolution of IGRA researches. Kekkaku, 2008, Vol. 83, no. 9, pp. 641-652.

4. Bell L.C.K., Breen R., Miller R.F., Noursadeghi M., Lipman M. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. International J. of Infectious Diseases, 2015, Vol. 32, pp. 39-45.

5. Dorhoi A., Kaufmann S.H. Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis. Semin. Immunopathol., 2015, Vol. 5, pp. 1-14.

6. Duque C., Arroyo L., Ortega H., Montufar F., Ortiz B., Rojas M., Barrera L.F. Different responses of human mononuclear phagocyte populations to Mycobacterium tuberculosis. J. Tuberculosis, 2014, Vol. 94, Issue 2, pp. 111-122.

7. Ferraz J.C., Melo F.B.S., Albuquerque M.F.P.M., Montenegro S.M.L., Abath F.G.C. Immune factors and immunoregulation in tuberculosis. Braz. J. Med. Biol. Res., 2006, Vol. 39, no. 11, pp. 1387-1397.

8. Flannagan R.S., Cosío G., Grinstein S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nature Reviews Microbiology, 2009, no. 7, pp. 355-366.

9. Hunter R.L. Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis (Edinburgh, Scotland), 2011, Vol. 91, no. 6, pp. 497-509.

10. Miranda M.S., Breiman A., Allain S., Deknuydt F., Altare F. The tuberculous granuloma: an unsuccessful host defence mechanism providing a safety shelter for the bacteria? Clinical and Developmental Immunology, 2012, Vol. 2012, pp. 1-14.

11. Ramachandra L., Smialek J. L., Shank S. S., Convery M., Boom W. H., Harding C. V. Phagosomal processing of Mycobacterium tuberculosis antigen 85b is modulated independently of mycobacterial viability and phagosome maturation. Infection and Immunity, 2005, Vol. 73, no. 2, pp. 1097-1105.

12. Sakamoto K. The Pathology of Mycobacterium tuberculosis infection. Veterinary Pathology, 2012, Vol. 49, no. 3, pp. 423-439.

13. Sakharova I.I., Ariél B.M., Skvortsova I.A., Knoring B.E., Vishnevski B.I., Aleshina G.M., Kokriakov V.N. Immunological parameters and mycobacterial biological properties in infiltrative pulmonary tuberculosis. Probl. Tuberk. Bolezn. Legk., 2005, no. 11, pp. 14-18.

14. Sharma S.K., Mohan A., Sharma A. Challenges in the diagnosis and treatment of miliary tuberculosis. Indian J. Med. Res, 2012, Vol. 135, no. 5, pp.703-730.

15. Tuberculosis / M. Monir Madkour, ed. Germany: Springer Science & Business Media, 2004. 930 p.

16. Ulrichs T., Kosmiadi G.A., Jörg S., Pradl L., Titukhina M., Mishenko V., Gushina N., Kaufmann S.H.E. Differential organization of the local immune response in patients with active cavitary tuberculosis or with nonprogressive tuberculoma. J. Infect. Dis., 2005, Vol. 192, no. 1, pp. 89-97.

17. Van Crevel R., Ottenhoff T.H.M., Van der Meer J.W.M. Innate Immunity to Mycobacterium tuberculosis. Clin. Microbiol. Rev., 2002, Vol. 15, no. 2, pp. 294-309.

18. Vergne I., Chua J., Singh S.B., Deretic V. Cell biology of Mycobacterium tuberculosis phagosome. Annu Rev. Cell Dev. Biol., 2004, Vol. 20, pp. 367-394.

19. Walzl G., Ronacher K., Hanekom W., Scriba T.J., Zumla A. Immunological biomarkers of tuberculosis. Nature Reviews Immunology, 2011, Vol. 11, pp. 343-354.

20. Wang Q, Liu S., Tang Y., Liu Q., Yao Y. MPT64 Protein from Mycobacterium tuberculosis inhibits apoptosis of macrophages through NF-kB-miRNA21-Bcl-2 pathway. J. Plos, 2014, Vol. 9, Issue 7, pp. 1-8.