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

Azevedo, Michelle de Campos Soriani; Marques, Heloisa; Binelli, Larissa Sarri; Malange, Mariana Silva Vieira; Devides, Amanda Carreira; Silva, Eliane Aparecida; Fachin, Luciana Raquel Vincenzi; Ghidella, Cássio César; Soares, Cléverson Teixeira; Garlet, Gustavo; Rosa, Patrícia Sammarco; Belone, Andréa de Faria Fernandes; Trombone, Ana Paula

doi:10.1007/s00430-017-0519-9

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…Also, immunostaining for different T reg cell markers and PCR to investigate the expression of different genes have also been described. T reg expression in leprosy reactions has been described in distinct body compartments either in situ T reg in biopsies of skin lesions or circulating systemic T reg in unstimulated fresh and in fresh or thawed stimulated cells [ 14 , 16 – 18 , 24 ]. Additionally, different antigen preparations have been used for culture stimulation (ML sonicate, PHA) [ 16 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Immunostaining in 96 leprosy lesions of different forms (Indeterminate/I, TT, BT, BB, BL, LL), T1R (n = 8) and T2R (n = 2) also found an increment of Foxp3 expression in T1R compared to unreactional lesions (I, BT and LL forms) [ 17 ]. Recently, the expression of cytokines related to T reg cell profile was evaluated by quantitative PCR in 87 skin biopsies from leprosy patients and showed decreased T reg cells markers in T1R and increased IL-17F, CCL20 and IL-8 in T2R when compared to the respective non-reactional leprosy patients [ 18 ].These apparently conflicting results are difficult to be compared may reflect the different methodological approaches and comparison groups used.…”

Section: Discussionmentioning

confidence: 99%

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In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions

et al. 2018

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Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves especially during immuno-inflammatory episodes known as type 1/T1R and type 2/T2R reactions. This study investigated the in situ expression of CD25+Foxp3+ Treg cells and TGF-β1, IFN-γ, IL-17 in leprosy T1R and T2R. Tregs were evaluated in 114 skin biopsies from 74 leprosy patients: 56 T1R (28-paired reaction-free/reactional biopsies, 28 unpaired T1R), 18 T2R (12 paired reaction-free/reactional biopsies, 6 unpaired T2R). Double CD25+Foxp3+immunostained Treg cells obtained by automated platform (Ventana BenchMark XT, Roche, Mannheim, Germany) were counted (Nikon Eclipse E400 2mm2). Cytokine expression was evaluated by immunostaining in 96 biopsies (48 paired reaction-free/reactional lesions, 24 T1R, 24 T2R) using rabbit polyclonal anti human TGF-β1, IFN-γ, IL-17 antibodies (Santa Cruz Biotechnology CA, USA). Treg cell counts in leprosy reactional lesions were higher compared to reaction-free (p = 0.002). Treg numbers were higher in T1R compared to paired unreactional T1R lesions (p = 0.001). Similar frequency of Treg was seen in paired reactional versus unreactional T2R lesions. Higher expression of TGF-β, IFN-γ and IL-17 was seen in T2R lesions compared to T1R and reaction-free lesions. The increase in Treg cells during T1R suggests a suppressive role to control the exacerbated cellular immune response during T1R that can cause tissue and nerve damage. Evidences of upregulated Treg cells in TR1, which usually occurs in patients with Th1-Th17 immunity and the indications of the expression of Th17/IL-17 in T2R, which develops in patients with Th2-Treg profile, suggest plasticity of Treg-Th17 cells populations and a potential role for these cell populations in the immunopathogenesis of leprosy reactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions

et al. 2018

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“…A higher IL‐10 production was also found in BALB/c mice at 8 months postinoculation compared to 5 months, suggesting an immunoregulatory role for IL‐10. The Treg cells were described as a population of CD4 + CD25 + FoxP3 + T cells that produce IL‐10 and TGF‐β characterized by innate and adaptive immune response regulation and in leprosy there are many studies showing the participation these cells . Thus, it is possible that the Treg cells are involved in the later phase of the infectious process (8 months postinoculation) in an attempt to limit the magnitude of the response to bacilly antigens and to prevent tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, studies showing the participation of regulatory T cells (Treg) in leprosy reported a higher expression of these cells in LL and BL patients, with increased production of IL‐10 and transforming growth factor‐β (TGF‐β), indicating the suppressor role of Treg cells in lepromatous leprosy . In addition to these cells, the participation of Th17 cells in TT/BT patients has been shown and reveals the predominance of cytokines related to the Th1/Th17 profile in the tuberculoid pole and Th2/Treg on the lepromatous pole …”

Section: Introductionmentioning

confidence: 99%

Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

Vilani-Moreno

Barbosa

Sartori

et al. 2019

Int J Experimental Path

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Summary This study evaluated the immune response of nude and BALB/c mice inoculated in the footpads (FP) with Mycobacterium leprae after 3, 5 and 8 months. At each timepoint peritoneal cells, peripheral blood, FP and popliteal lymph nodes (PLN) were collected. Peritoneal cell cultures were performed to measure the H2O2, O2−, NO, IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ and TNF levels. Serum levels of anti‐PGL‐I antibodies were also quantified. The results showed that the infection was progressive in nude mice with bacterial multiplication, development of macroscopic lesions in the FP and presence of bacilli in the PLN at 8 months. In BALB/c mice, the infection reached a plateau of bacillary multiplication at 5 months and regressed at 8 months. Histopathological analysis of FP revealed a mononuclear inflammatory infiltrate with a large number of neutrophils at 5 months, with a higher number in nude mice. At 8 months, the number of neutrophils decreased and the infiltrate was predominantly mononuclear in both mouse strains. There was no H2O2, O2−, IL‐2, IL‐4, IL‐10 and IFN‐γ production in the course of infection in nude mice; however, in BALB/c, O2− and IL‐12 production was higher at 5 months and NO, IFN‐γ and TNF production was higher at 8 months when there was a decrease in the number of bacilli. The level of anti‐PGL‐I antibodies was higher in BALB/c mice. Thus, nude and BALB/c mice can be used as experimental models for the study of various aspects of leprosy.

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“…3,5,6 More recent studies have also indicated the involvement of Th17 cells with elevated levels of interleukin-17 in culture supernatants and skin lesions; 7-9 however, no significant change in serum levels of interleukin-17 was observed in ENL. [10][11][12] Given the importance of finding clinical and laboratory markers that recognize both ENL patients and those at increased risk of ENL development, the objective of our study was to evaluate serum mediators of innate and adaptive immune responses, including both pro and anti-inflammatory cytokines, to identify laboratory markers for ENL.…”

Section: Introductionmentioning

confidence: 99%

Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker

Vilani-Moreno¹,

Souza

Silva

et al. 2021

IJDVL

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Background: Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. Aims: The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. Methods: The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). Results: Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. Limitations: Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. Conclusion: High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.

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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

Cited by 13 publications

References 39 publications

In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions

In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions

Murine experimental leprosy: Evaluation of immune response by analysis of peritoneal lavage cells and footpad histopathology

Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker

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