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Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events

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Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

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Acknowledgements

This study was supported by Grants from Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (2009/06122-5).

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Author notes

  1. Michelle de Campos Soriani Azevedo and Heloisa Marques contributed equally to this study.

Authors and Affiliations

  1. Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, Bauru, São Paulo, 17034-971, Brazil

    Michelle de Campos Soriani Azevedo, Eliane Aparecida Silva, Luciana Raquel Vincenzi Fachin, Cleverson Teixeira Soares, Patrícia Sammarco Rosa & Andrea de Farias Fernandes Belone

  2. Centro de Ciências da Saúde, Universidade do Sagrado Coração, Rua Irmã Arminda, 10-50, Jardim Brasil, Bauru, São Paulo, 17.011-160, Brazil

    Heloisa Marques, Larissa Sarri Binelli, Mariana Silva Vieira Malange, Amanda Carreira Devides & Ana Paula Favaro Trombone

  3. Centro de Referência de Hanseníase e Tuberculose, Rua Pedro Guimarães s/n, Bairro Santa Cruz, Rondonópolis, Mato Grosso, 78710-760, Brazil

    Cassio Cesar Ghidella

  4. Departamento de Ciências Biológicas, Faculdade de Odontologia de Bauru, Universidade de São Paulo, Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, São Paulo, 17012-901, Brazil

    Gustavo Pompermaier Garlet

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  1. Michelle de Campos Soriani Azevedo
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Correspondence to Ana Paula Favaro Trombone.

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Azevedo, M.d.S., Marques, H., Binelli, L.S. et al. Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events. Med Microbiol Immunol 206, 429–439 (2017). https://doi.org/10.1007/s00430-017-0519-9

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