Lsr2 of Mycobacterium leprae and Its Synthetic Peptides Elicit Restitution of T Cell Responses in Erythema Nodosum Leprosum and Reversal Reactions in Patients with Lepromatous Leprosy

Saini, Chaman; Prasad, H. K.; Rani, Rajni; Murtaza, Anwar; Misra, Namita; Narayan, N P; Nath, Indira

doi:10.1128/cvi.00762-12

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Cytokines associated with Th1 and Th2 subsets showed fold change increases in both reactions. Whereas RR showed increase in both Th1[ 32 ] and Th2 cytokines, ENL showed significant fold change increase only in IFN-γ as reported earlier[ 8 ].…”

Section: Resultssupporting

confidence: 80%

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Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Saini

Siddiqui²,

Ramesh

et al. 2016

PLoS Negl Trop Dis

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Background50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.Methodology and Principle FindingsQuantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.ConclusionsPatients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.

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Section: Resultssupporting

confidence: 80%

“…The triggering factors in the inductions of these reactions are not known although motifs of LSR2protein of M . leprae have been shown to be recognized during ENL[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Saini

Siddiqui²,

Ramesh

et al. 2016

PLoS Negl Trop Dis

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“…An elevated level of IL-4, IL-6, and IL-8 has also been reported in leprosy [ 100 ]. Hence, there is a temporary augmentation of T-cell responses in LL patients, which keeps on going even after a drop in clinical features [ 101 ].…”

Section: Reviewmentioning

confidence: 99%

Leprosy Classification, Clinical Features, Epidemiology, and Host Immunological Responses: Failure of Eradication in 2023

Alrehaili

2023

Cureus

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Leprosy is of big concern in the medical fraternity. Leprosy is also known as Hansen’s disease. It is a curable communicable disease that remains prevalent in most countries all over the globe. It is a chronic granulomatous infection commonly caused by Mycobacterium leprae and Mycobacterium lepromatosis , which mainly show an effect on the skin and peripheral nerves. To control the disease and minimize the impact of the disease, much effort has been put into it for decades. Nearly 0.2 million fresh cases were documented in 2017 worldwide in spite of being declared “eradicated” by the WHO in the year 2000. However, impressive achievements have been made in several countries, including India; still, we are lagging behind the ultimate goal of the final disappearance of leprosy. Extensive migration is a crucial element that may transmit leprosy to unaffected areas. Additionally, there are several areas in the USA where person-to-person leprosy transmission has been reported without a prior history of exposure. Recently, WHO instigated a new Global Leprosy Strategy 2021-2030, termed "Towards Zero Leprosy." In this article, we review the clinical features, leprosy epidemiology, transmission, classification, host immunological response, and diagnostic challenges.

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“…CD4 + T cells differentiate according to the microenvironment into Th1, Th2 cells, or subsets of Th17 and Treg ( 104 ). Recent studies have reported the frequency of the newly described Th17 and Treg subsets in leprosy ( 105 , 106 ). Using flow cytometry in ENL, the absolute numbers and proportion of Tregs were shown to be significantly lower during ENL although FoxP3 expression, a marker they used to define Tregs, was higher ( 107 ).…”

Section: What Is the Role Of T-cells In Enl?mentioning

confidence: 99%

A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum

2017

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Erythema nodosum leprosum (ENL) is a painful inflammatory complication of leprosy occurring in 50% of lepromatous leprosy patients and 5–10% of borderline lepromatous patients. It is a significant cause of economic hardship, morbidity and mortality in leprosy patients. Our understanding of the causes of ENL is limited. We performed a systematic review of the published literature and critically evaluated the evidence for the role of neutrophils, immune complexes (ICs), T-cells, cytokines, and other immunological factors that could contribute to the development of ENL. Searches of the literature were performed in PubMed. Studies, independent of published date, using samples from patients with ENL were included. The search revealed more than 20,000 articles of which 146 eligible studies were included in this systematic review. The studies demonstrate that ENL may be associated with a neutrophilic infiltrate, but it is not clear whether it is an IC-mediated process or that the presence of ICs is an epiphenomenon. Increased levels of tumor necrosis factor-α and other pro-inflammatory cytokines support the role of this cytokine in the inflammatory phase of ENL but not necessarily the initiation. T-cell subsets appear to be important in ENL since multiple studies report an increased CD4+/CD8+ ratio in both skin and peripheral blood of patients with ENL. Microarray data have identified new molecules and whole pathophysiological pathways associated with ENL and provides new insights into the pathogenesis of ENL. Studies of ENL are often difficult to compare due to a lack of case definitions, treatment status, and timing of sampling as well as the use of different laboratory techniques. A standardized approach to some of these issues would be useful. ENL appears to be a complex interaction of various aspects of the immune system. Rigorous clinical descriptions of well-defined cohorts of patients and a systems biology approach using available technologies such as genomics, epigenomics, transcriptomics, and proteomics could yield greater understanding of the condition.

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Lsr2 of Mycobacterium leprae and Its Synthetic Peptides Elicit Restitution of T Cell Responses in Erythema Nodosum Leprosum and Reversal Reactions in Patients with Lepromatous Leprosy

Cited by 10 publications

References 39 publications

Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Leprosy Classification, Clinical Features, Epidemiology, and Host Immunological Responses: Failure of Eradication in 2023

A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum

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