T Regulatory Cells and Plasmocytoid Dentritic Cells in Hansen Disease: A New Insight Into Pathogenesis?

Massone, Cesare; Nunzi, Enrico; Ribeiro‐Rodrigues, Rodrigo; Talhari, Carolina; Talhari, Sinésio; Schettini, Antônio Pedro Mendes; Parente, José Napoleão Tavares; Brunasso, Alexandra Maria Giovanna; Puntoni, Matteo; Clapasson, Andrea; Noto, Salvatore; Cerroni, Lorenzo

doi:10.1097/dad.0b013e3181b7fc56

Cited by 33 publications

(44 citation statements)

References 29 publications

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“…FoxP3+ Tregs have also been previously detected in biopsies of leprosy patients. 22 However, no statistical differences between Tregs frequency in the distinct categories of patients could be detected in that study, probably because of the limited number of patients within each category of the leprosy spectrum. Moreover, neither in situ double staining (CD25+/FoxP3+) nor appropriate quantitative imaging analysis could be performed in this study.…”

Section: Discussionmentioning

confidence: 53%

“…Moreover, neither in situ double staining (CD25+/FoxP3+) nor appropriate quantitative imaging analysis could be performed in this study. 22 We also showed that the increased expression of Tregs was paralleled by higher in situ expression of CTLA-4 and IL-10 but not TGF-β, suggesting potential mechanisms by which these cells could suppress CD4+ T cell responses. Although several studies verified the in vitro immunosuppressive ability of Tregs isolated from sites of disease, the mechanisms through which Tregs exerted this ability remained to be determined.…”

Section: Discussionmentioning

confidence: 72%

“…21,22 We show here that Tregs are present in increased numbers and may have a pathogenic role in leprosy patients harboring uncontrolled bacillary multiplication (lepromatous leprosy) but not in those individuals capable of limiting M. leprae growth (tuberculoid leprosy). Increased frequency of CD25+ FoxP3+ T cells was seen both in in vitro M. leprae-stimulated PBMCs and disease sites.…”

Section: Discussionmentioning

confidence: 97%

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Increased Expression of Regulatory T Cells and Down-Regulatory Molecules in Lepromatous Leprosy

Palermo¹,

Pagliari²,

Trindade³

et al. 2012

The American Journal of Tropical Medicine and Hygiene

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Abstract. T regulatory cells (Tregs) play an important role in the mechanism of host's failure to control pathogen dissemination in severe forms of different chronic granulomatous diseases, but their role in leprosy has not yet been elucidated; 28 newly diagnosed patients (16 patients with lepromatous leprosy and 12 patients with tuberculoid leprosy) and 6 healthy Mycobacterium leprae-exposed individuals (contacts) were studied. Tregs were quantified by flow cytometry (CD4+ CD25+ Foxp3+) in peripheral blood mononuclear cells stimulated in vitro with a M. leprae antigenic preparation and phytohemagglutinin as well as in skin lesions by immunohistochemistry. The lymphoproliferative (LPR), interleukin-10 (IL-10), and interferon-γ (IFN-γ) responses of the in vitro-stimulated peripheral blood mononuclear cells and the in situ expression of IL-10, transforming growth factor-β (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were also determined. We show that M. leprae antigens induced significantly lower LPR but significantly higher Treg numbers in lepromatous than tuberculoid patients and contacts. Mitogen-induced LPR and Treg frequencies were not significantly different among the three groups. Tregs were also more frequent in situ in lepromatous patients, and this finding was paralleled by increased expression of the antiinflammatory molecules IL-10 and CTLA-4 but not TGF-β. In lepromatous patients, Tregs were intermingled with vacuolized hystiocyte infiltrates all over the lesion, whereas in tuberculoid patients, Tregs were rare. Our results suggest that Tregs are present in increased numbers, and they may have a pathogenic role in leprosy patients harboring uncontrolled bacillary multiplication but not in those individuals capable of limiting M. leprae growth.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 97%

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Increased Expression of Regulatory T Cells and Down-Regulatory Molecules in Lepromatous Leprosy

Palermo¹,

Pagliari²,

Trindade³

et al. 2012

The American Journal of Tropical Medicine and Hygiene

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“…Only a small percentage (o1%) of the population that comes into contact with M. leprae will develop the disease, providing an extraordinary opportunity to study resistance versus susceptibility to a microbial pathogen. Additionally, the large spectrum of disease is highly dependent on the type of immune response developed by the host to the infection, providing a good model to understand pathogenesis mechanisms [Gulia et al, 2010;Massone et al, 2010]. This review will outline the current epidemiological and clinical situation regarding leprosy, with particular emphasis on a leprosy referral center in Sergipe, Brazil.…”

Section: Introductionmentioning

confidence: 98%

Clinical, immunological, and genetic aspects in leprosy

Simon

Scherlock

Duthie

et al. 2011

Drug Development Research

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Leprosy is a chronic infection caused by Mycobacterium leprae. It affects the skin and peripheral nerves and can cause irreversible chronic disabilities. The worldwide registered number of cases in 2009 was 213,036. This review discusses clinical aspects of the disease, including leprosy reactions and neuronal damage, as well as immunological and immunogenetic aspects influencing disease susceptibility and outcome. The cardinal signs of leprosy are skin lesions with altered sensation, thickened peripheral nerves, and presence of alcohol acid-resistant bacilli in skin biopsy or lymph. Confirmatory examinations include (1) bacteriological examination, which allows patients' classification into two operational groups, multibacillary (MB) and paucibacillary (PB); and (2) histopathological examination, which permits stratification in different clinical forms. These clinical forms differ not only by histopathology but also according to the host's immune response to M. leprae. These forms comprise the extremes of (1) tuberculoid leprosy (TT), with a specific Th1 response and control of M. leprae multiplication; (2) lepromatous leprosy (LL) without Th1 response and preserved Th2 response; and (3) the interpolar clinical forms, borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), and indeterminate form (IL). Appropriate treatment is based on smear examination or the number of lesions at diagnosis. In the evolution of leprosy, acute inflammation, known as reactions, may occur during or after treatment. These reactions are classified into two main types: the type I reaction or reversal reaction (RR), and the type II reaction or erythema nodosum leprosum (ENL). The role of innate immune response to control the infection is supported by immunological and genetic studies. Drug Dev Res 72:509-527, 2011.

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“…At this exact point, the CMI plays a pivotal role. Subjects with a predominant Th1 immune response will develop a high degree of CMI with epithelioid granuloma formation that will destroy all the bacilli with either healing or development of localized disease (tuberculoid leprosy, TT) [9]. TT has a short incubation time (2-3 years) and remains circumscribed to skin and nerves of a limited area of the body.…”

mentioning

confidence: 99%