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Evaluation of the regulatory T and Th17 cells role in the human and experimental leprosy: correlation with leprosy spectrum, metalloproteinases and their inhibitors expression, and interaction with Th1/Th2 paradigm

Abstract

Leprosy is a chronic infectious disease of the skin and peripheral nerves caused by Mycobacterium leprae. This bacillus is obligate intracellular parasite with tropism for Schwann cells and macrophages, whose optimal growth occurs at 27ºC - 30ºC being responsible for the occurrence of the leprosy in superficial and cooler areas such skin, nerves, testis and upper respiratory tract. The individuals that develop clinical leprosy can be classified in a five group spectrum [tuberculoid tuberculoid (TT), lepromatous leprosy (LL), borderline tuberculoid (BT), borderline borderline (BB) e borderline lepromatous (BL)], depending on disease dissemination and the pattern of immune response, and in addition, superimposed on the leprosy spectrum, leprosy reactions can occur (type 1 and type 2). Analyzing all the groups (polar and borderlines) and leprosy reactions was observed that Th1 and Th2 patterns were involved with disease outcome, but this Th1/Th2 model not fully correspond with disease pathogenesis. Therefore, this study will evaluate the participation of the regulatory T cells and Th17 cells in the leprosy pathogenesis, and in addition will investigate the involvement of the matrix metalloproteinases (MMP-2 e MMP-9) and TIMPs (TIMP-1, TIMP-2 and TIMP-3) in skin lesions, since at the moment the studies have evaluation only cytokine pattern related with Th-1/Th-2 paradigm. This approach will contribute to understanding of the immunoregulation of this disease, and the expected results will potentially contribute to improve leprosy diagnosis and the development of new therapeutic strategies.Leprosy is a chronic infectious disease of the skin and peripheral nerves caused by Mycobacterium leprae. This bacillus is obligate intracellular parasite with tropism for Schwann cells and macrophages, whose optimal growth occurs at 27ºC - 30ºC being responsible for the occurrence of the leprosy in superficial and cooler areas such skin, nerves, testis and upper respiratory tract. The individuals that develop clinical leprosy can be classified in a five group spectrum [tuberculoid tuberculoid (TT), lepromatous leprosy (LL), borderline tuberculoid (BT), borderline borderline (BB) e borderline lepromatous (BL)], depending on disease dissemination and the pattern of immune response, and in addition, superimposed on the leprosy spectrum, leprosy reactions can occur (type 1 and type 2). Analyzing all the groups (polar and borderlines) and leprosy reactions was observed that Th1 and Th2 patterns were involved with disease outcome, but this Th1/Th2 model not fully correspond with disease pathogenesis. Therefore, this study will evaluate the participation of the regulatory T cells and Th17 cells in the leprosy pathogenesis, and in addition will investigate the involvement of the matrix metalloproteinases (MMP-2 e MMP-9) and TIMPs (TIMP-1, TIMP-2 and TIMP-3) in skin lesions, since at the moment the studies have evaluation only cytokine pattern related with Th-1/Th-2 paradigm. This approach will contribute to understanding of the immunoregulation of this disease, and the expected results will potentially contribute to improve leprosy diagnosis and the development of new therapeutic strategies. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SORIANI AZEVEDO, MICHELLE DE CAMPOS; MARQUES, HELOISA; BINELLI, LARISSA SARRI; VIEIRA MALANGE, MARIANA SILVA; DEVIDES, AMANDA CARREIRA; SILVA, ELIANE APARECIDA; VINCENZI FACHIN, LUCIANA RAQUEL; GHIDELLA, CASSIO CESAR; SOARES, CLEVERSON TEIXEIRA; GARLET, GUSTAVO POMPERMAIER; ROSA, PATRICIA SAMMARCO; FERNANDES BELONE, ANDREA DE FARIAS; FAVARO TROMBONE, ANA PAULA. 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. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 206, n. 6, p. 429-439, DEC 2017. Web of Science Citations: 2.
MICHELLE DE CAMPOS SORIANI AZEVEDO; NATÁLIA MORTARI RAMUNO; LUCIANA RAQUEL VINCENZI FACHIN; MÔNICA TASSA; PATRÍCIA SAMMARCO ROSA; ANDREA DE FARIA FERNANDES BELONE; SUZANA MADEIRA DIÓRIO; CLEVERSON TEIXEIRA SOARES; GUSTAVO POMPERMAIER GARLET; ANA PAULA FAVARO TROMBONE. qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms. Brazilian Journal of Infectious Diseases, v. 21, n. 1, p. 71-78, Fev. 2017. Web of Science Citations: 5.
FAVARO TROMBONE, ANA PAULA; BARBOSA PEDRINI, SILVIA CRISTINA; DIORIO, SUZANA MADEIRA; FERNANDES BELONE, ANDREA DE FARIA; VICENZI FACHIN, LUCIANA RAQUEL; DO NASCIMENTO, DEJAIR CAITANO; ROSA, PATRICIA SAMMARCO. Optimized Protocols for Mycobacterium leprae Strain Management: Frozen Stock Preservation and Maintenance in Athymic Nude Mice. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 85 MAR 2014. Web of Science Citations: 1.

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