Identification of a systemic interferon- γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction

by Rosane M. B. Teles, Jing Lu, Maria Ti ó-Coma, Isabela M. B. Goulart, Sayera Banu, Deanna Hagge, Kidist Bobosha, Tom Ottenhoff, Matteo Pellegrini, Annemieke Geluk, Robert L. Modlin Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacteriumMycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes,bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN- γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in thebisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically,GBP1,GBP2,GBP3 andGBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, withGBP1,GBP2 andGBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemi...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research

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AbstractLeprosy is a chronic infectious disease of the skin and peripheral nerves that presents a strong link with the host genetic background. Different approaches in genetic studies have been applied to leprosy and today leprosy is  among the infectious diseases with the greatest number of genetic risk variants identified. Several leprosy genes have been implicated in host immune response to pathogens and point to specific pathways that are relevant for host defense to infection. In addition, host genetic factors are also inv olved in the heterogeneity of leprosy clinical manifestations and in excessive inflammatory...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research
We report a case of resistant bacilli in late reaction and discuss the implications of this finding. PMID: 31707970 [PubMed - as supplied by publisher]
Source: Tropical Doctor - Category: Tropical Medicine Authors: Tags: Trop Doct Source Type: research
In 2013, Lepra Bangladesh (a non-government organization) and the National Leprosy Programme of the Directorate General of Health Services under the Ministry of Health and Family Welfare, Bangladesh implemente...
Source: BMC Health Services Research - Category: General Medicine Authors: Tags: Research article Source Type: research
Authors: Thangaraju P, Venkatesan AS PMID: 31665397 [PubMed - as supplied by publisher]
Source: Military Medicine - Category: International Medicine & Public Health Tags: Mil Med Source Type: research
by Diana N. J. Lockwood, Saba Lambert, Aparna Srikantam, Joydeepa Darlong, V. V. Pai, C. Ruth Butlin, Barbara de Barros, Edessa Negera, Stephen L. Walker
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Authors: Pradana KA, Widjaya MA, Wahjudi M Abstract In Human, Major Histocompatibility Complex known as Human Leukocyte Antigen (HLA). The HLA grouped into three subclasses regions: the class I region, the class II region, and the class III region. There are thousands of polymorphic HLAs, many of them are proven to have correlations with diseases. Indonesia consists of diverse ethnicity people and populations. It carries a unique genetic diversity between one and another geographical positions. This paper aims to extract Indonesians HLA allele data, mapping the data, and correlating them with global diseases. From ...
Source: Immunological Investigations - Category: Allergy & Immunology Tags: Immunol Invest Source Type: research
ABSTRACT This paper reviews aspects of the life and work of Professor Louis Ranvier 140 years after the publication of Le çons sur l ’ histologie du syst ème nerveux, published in 1878, and shows the importance of the histological description of myelinated fibers of the nodes of Ranvier.RESUMO Os autores apresentam uma revis ão sobre aspectos da vida e obra do Professor Louis Ranvier 140 anos após a publicação de seu livro Leçons sur l ’ histologie du syst ème nerveux publicado em 1878 e mostra a importância da descrição histológ...
Source: Arquivos de Neuro-Psiquiatria - Category: Neurology Source Type: research
DiscussionEven in this previously highly VL endemic area, PKDL is a rare condition. Nevertheless, even a single case can trigger a new VL outbreak. Leprosy is also a rare disease, but current prevalence is over 17 times the elimination threshold proclaimed by WHO. Both diseases require continued surveillance. Active case finding for leprosy can be recommended among household members and close neighbors of leprosy patients but would not be feasible for entire populations. Periodic skin camps may be a feasible and affordable alternative.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease. PMID: 31633447 [PubMed - as supplied by publisher]
Source: International Reviews of Immunology - Category: Allergy & Immunology Tags: Int Rev Immunol Source Type: research
Abstract In Type II lepromatous reaction, there is exacerbation of humoral immunity, classified as Gell &Coombs Type III hypersensitivity reaction. It is more common in lepromatous borderline (LB) and lepromatous lepromatous (LL) patients. Our objective was to study the clinical and laboratorial expressions of lepromatous Type II reactions, establishing concordances between them, and for this the medical records of leprosy patients observed at the Clementino Fraga Filho University Hospital of the Federal University of Rio de Janeiro (HUCFF/UFRJ) were reviewed. There were a total of 358 leprosy cases over a per...
Source: Skinmed - Category: Dermatology Authors: Tags: Skinmed Source Type: research
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