Acta Medica Iranica 2018. 56(8):484-493.

Mycobacterium Tuberculosis Infection: Participation of TH1, TH2, TH17 and Regulatory T Cells in the Immune Response
Gerardo Fernando Fernández Soto, Nereida Valero Cedeño, Carolina Arráiz de Fernández, Patricia Paredes Lascano, Miriam Fernández Nieto, María Teresa Peñaherrera Ron

Abstract


Mycobacterium tuberculosis, the etiologic agent of Tuberculosis, is a pathogen that is widely distributed geographically. Tuberculosis is classified as a granulomatous inflammatory condition where effector cells accumulate at the site of mycobacterial infection to form the characteristic tubercle. Regulating proteins of Th1 and Th17 cells participate  in the formation of Mycobacterium-induced granuloma. The predominance of Th2 phenotype cytokines increases the severity of Tuberculosis. Treg cells are increased in patients with active Tuberculosis but decrease with anti-Tuberculosis treatment. The increment of these cells causes down-regulation of adaptive immune response facilitating the persistence of the bacterial infection. Mycobacterium tuberculosis-induced Treg cells to secrete cytokines that inhibit the immune response. This has been considered an important evasion mechanism although it is not the only that intervenes. The evolution of the Mycobacterium tuberculosis infection will depend on the cytokines' network that traduces pathological change in cells and tissues which explain the clinical manifestations existing in affected patients.


Keywords


Mycobacterium tuberculosis; Virulence; Host genetic; Immune response; Cytokines

Full Text:

PDF

References


References

Romero Adrián TB, Leal Montiel J, Fernández G, Valecillo A. Role of cytokines and other factors involved in the Mycobacterium tuberculosis infection. World J Immunology. 2015;27:16-50

Frieden TR, Sterling TR, Munsiff SS. Tuberculosis. Lancet. 2003; 362: 887-99

Wan YY, Flavell RA. How diverse- CD4 effector Tcells and their functions. J Mol Cell Biol. 2009;1:20-36

Rozot V, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, Perreau M, et al. Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol. 2013; 43(6):1568-77.

Sasindran SJ, Torrelles JB. Mycobacterium Tuberculosis Infection and Inflammation: what is Beneficial for the Host and for the Bacterium? . Frontiers in Microbiology. 2011; 2:2.

Moreira-Teixeira L, Sousa J, McNab FW, et al. Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling. The Journal of Immunology Author Choice. 2016; 197(12):4714-4726.

Bell LCK, Pollara G, Pascoe M, Gillian S. Tomlinson, Rannakoe J., et al. In Vivo Molecular Dissection of the Effects of HIV-1 in Active Tuberculosis. Fortune SM, ed. PLoS Pathogens. 2016; 12(3):e1005469.

Senait Ashenafi, Getachew Aderaye, Amsalu Bekele, Martha Zewdie, Getachew Aseffa, Anh Thu Nguyen Hoang, et al. Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3. Clinical Immunology.2014; 151 (2):84-89

Amelio P, Portevin D, Reither K, Mhimbira F, Mpina M, Tumbo A, et al. Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania. Babu S, ed. PLoS Neglected Tropical Diseases. 2017; 11(7):e0005817.

Freeman S, Post FA, Bekker LG, Harbacheuski R, Steyn LM, Ryffel B, et al. tuberculosis H37Ra and H37Rv differential growth and cytokine/chemokine induction in murine macrophages in vitro. J. Interferon Cytokine Res. 2006;26:27-33

Surewicz K, Aung H, Kanost RA, Jones L, Hejal R, Toossi Z. The differential interaction of p38 MAP kinase and tumor necrosis factor-alpha in human alveolar macrophages and monocytes induced by Mycobacterium tuberculosis. Cell Immunol. 2004;228:34-41

Sun Y J, Lim T K, Ong A K, Ho B C, Seah G T, Paton N I. Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison. BMC Infect Dis. 2006;6:105

Romero Adrián TB, Leal Montiel J, Monsalve-Castillo F, Mengual Moreno E, Ernesto García, McGregor E, et al. Helicobacter pylori: Bacterial factors and the role of cytokines in the immune response. Curr Microbiol. 2010;60:143-155

George PJ, Anuradha R, Kumaran PP, Chandrasekaran V, Nutman TB, Babu S. Modulation of mycobacterial-specific Th1 and Th17 cells in latent tuberculosis by coincident hookworm infection. J Immunol. 2013;190:5161-5168

Zuñiga J, Torres García D, Santos Mendoza T, Rodríguez Reyna TS, Granados J, Yunis EJ. Cellular and humoral mechanisms involved in the control of tuberculosis. Clin Dev Immunol. 2012;2012:193923

Wang F, Mao L, Hou H, Wu S, Huang M, Yin B, et al. The source of Mycobacterium tuberculosis-specific IFN-γ production in peripheral blood mononuclear cells of TB patients. Int Immunopharmacol. 2016; 32:39-45.

Pollock KM, Montamat-Sicotte DJ, Grass L, Cooke GS, Kapembwa MS, Kon OM, et al. PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection. PLoS One. 2016. 12; 11(1):e0146905.

Winslow GM, Cooper A, Reiley W, Chatterjee M, Woodland DL. Early T-cell responses in tuberculosis immunity. Immunological reviews.2008; 225:10.1111/j. 1600-065X.2008.00693.

Herzmann C, Ernst M, Ehlers S, Stenger S, Maertzdorf J, Sotgiu G, Lange C. Increased frequencies of pulmonary regulatory T-cells in latent Mycobacterium tuberculosis infection. Eur Respir J. 2012; 40(6):1450-7.

Ribeiro-Rodrigues R, Resende Co T, Rojas R, Z Toossi, R Dietze, W H Boomet, et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clinical and Experimental Immunology. 2006; 144(1):25-34.

Diniz LM, Zandonade E, Dietze R, Pereira FE, Ribeiro-Rodrigues R. Short report: do intestinal nematodes increase the risk for multibacillary leprosy? Am J Trop Med Hyg. 2001;65:852-854

Arango Duque G, Descoteaux A. Macrophage Cytokines: Involvement in Immunity and Infectious Diseases. Frontiers in Immunology. 2014; 5:491.

Pinheiro RO, de Oliveira EB, Dos Santos G, Sperandio da Silva GM, de Andrade Silva BJ, et al. Immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients. Clin Exp Immunol. 2013; 171(2):210-9.

Hossain MM, Norazmi M-N. Pattern Recognition Receptors and Cytokines in Mycobacterium tuberculosis Infection-The Double-Edged Sword?. Bio Med Research International. 2013; 2013:179174.

Redford PS, Murray PJ, O'Garra A. The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol. 2011; 4(3):261-70.

Kumar NP, Anuradha R, Suresh R, Ganesh R, Shankar J, Kumaraswami V. Suppressed type 1, type 2, and type 17 cytokine responses in active tuberculosis in children. Clin Vaccine Immunol. 2011;18:1856-64

Weiner H.L. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol Rev. 2001;182:207-214

Vieira PL, Christensen JR, Minaee S, O'Neill EJ, Barrat FJ, Boonstra A, , et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4 + CD25+ regulatory T cells. J Immunol 2004;172:5986-5993

Singh A, Dey AB, Mohan A, Sharma PK, Mitra DK. Foxp3+ Regulatory T Cells among Tuberculosis Patients: Impact on Prognosis and Restoration of Antigen Specific IFN-γ Producing T Cells. PLoS ONE. 2012;7:e44728

Quinn KM, McHugh RS, Rich FH, Goldsack LM, de Lisle GW, Buddle BM , et al. Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol Cell Bio. 2006;184:467-474

Scott-Browne JP, Shafiani S, Tucker-Heard G, Ishida-Tsubota K, Fontenot DJ, Rudensky AY, et al. Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Med. 2007;204:2159-2169

Ribeiro-Rodrigues R, Resende Co T, Rojas R, Toossi Z, Dietze R, Boom WH, et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clin Exp Immunol. 2006;144:25-44

Larson RP, Shafiani S, Urdahl KB. Foxp3(+) regulatory T cells in tuberculosis. Adv Exp Med Biol. 2013;783:165-180

Romero-Adrián T, Leal- Montiel J. Helicobacter pylori infection: Regulatory T cells and participation in the Regulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosis. Tuberculosis. immune response. Jundishapur J Microbiol. 2013;6:e5183

Marin ND, París SC, Vélez VM, Rojas CA, Rojas M, García LF. 2010;90:252-261

De Almeida AS, Fiske CT, Sterling TR, Kalams SA. Increased frequency of regulatory T cells and T lymphocyte activation in persons with previously treated extrapulmonary tuberculosis. Clin Vaccine Immunol. 2012;19:45-52

Rahman S, Gudetta B, Fink J, Granath A, Ashenafi S, Aseffa A, et al. Compartmentalization of immune responses in human tuberculosis: few CD8+ effector T cells but elevated levels of FoxP3+ regulatory T cells in the granulomatous lesions. Am J Pathol. 2009;174:2211-2224

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

Korb VC, Chuturgoon AA, Moodley D. Mycobacterium tuberculosis: Manipulator of Protective Immunity. Int J Mol Sci. 2016; 17:131.

Cumming BM, Rahman MA, Lamprecht DA, Rohde KH, Saini V, Adamson JH, et al. Mycobacterium tuberculosis arrests host cycle at the G1/S transition to establish long term infection. PLoS Pathog. 2017; 13:e1006389.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.