Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy

Leprosy is a chronic disease caused by M. leprae infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant M. leprae antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts (M. leprae cell sonicate–MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of M. tuberculosis Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against M. leprae infection that prevents the development of leprosy. These data further our understanding of M. leprae infection/leprosy and are instructive for vaccine development

sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-05T13:29:54Z No. of bitstreams: 1 Silva LR sCD163 levels as a biomarker of disease....pdf: 1813439 bytes, checksum: 61b593e582b8cc501964a9d141747a1a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-05T13:58:17Z (GMT) No. of bitstreams: 1 Silva LR sCD163 levels as a biomarker of disease....pdf: 1813439 bytes, checksum: 61b593e582b8cc501964a9d141747a1a (MD5)Made available in DSpace on 2018-04-05T13:58:17Z (GMT). No. of bitstreams: 1 Silva LR sCD163 levels as a biomarker of disease....pdf: 1813439 bytes, checksum: 61b593e582b8cc501964a9d141747a1a (MD5) Previous issue date: 2017Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (FAPITEC - http://www.fapitec.se.gov.br/)/SE/FUNTEC/Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Grants: CNPq n.12/2009, Processo n. 019.203.02712/2009-8 (ARJ).Universidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil / Universidade Federal de Sergipe. Departamento de Educação em Saúde de Lagarto. Lagarto, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil / Universidade Federal de Sergipe. Departamento de Educação em Saúde de Lagarto. Lagarto, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil / Universidade Federal de Sergipe. Departamento de Educação em Saúde de Lagarto. Lagarto, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, Brasil / Universidade Federal de Sergipe. Departamento de Educação em Saúde de Lagarto. Lagarto, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Bioquímica e Imunologia. Ribeirão Preto, SP, BrasilHoward University. Department of Biology. Washington, DC, USAInfectious Diseases Research Institute. Seattle, WA, USAInfectious Diseases Research Institute. Seattle, WA, USAUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Laboratório de Biologia Molecular. Aracaju, SE, BrasilCD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens