Evaluation of cellular immune response in patients with recurrent candidiasis

A candidíase recorrente cutânea ou mucosa é caracterizada pela ocorrência de, no mínimo, 4 episódios de candidíase no período de um ano. Não são conhecidos os fatores que levam à recorrência desta infecção. O presente estudo avaliou a resposta linfoproliferativa e a produção de IFN-g de pacientes com candidíase recorrente. Os índices de estimulação da resposta linfoproliferativa em culturas de células de pacientes com candidíase recorrente estimuladas com antígeno de Candida albicans, PPD e TT foram respectivamente de 6±8, 17±20 e 65±30. A adição de anticorpo monoclonal anti-IL-10 às culturas de células de 6 pacientes aumentou a resposta linfoproliferativa de 735±415 para 4143±1746 cpm. A produção de IFN-g em culturas de células estimuladas com antígeno de Candida, foi 162±345pg/ml. Pacientes com candidíase recorrente apresentam uma deficiência na resposta linfoproliferativa e na produção de IFN-g, podendo a resposta imune celular ao antígeno de Candida ser restaurada parcialmente através da neutralização da IL-10 in vitro. _________________________________________________________________________________________ ABSTRACT: Recurrent cutaneous or mucosal candidiasis is characterized by the occurrence of at least four candidiasis episodes within a one-year period. The factors involved in recurrence of infection are still unknown. In the present study the lymphoproliferative response and the IFN-g production by candidiasis patients were evaluated. The stimulation index of mononuclear cell cultures of candidiasis patients stimulated with Candida albicans antigen, PPD and TT were 6±8, 17±20 and 65±30, respectively. The addition of monoclonal antibody anti-IL-10 to Candida albicans antigen stimulated cultures raised the lymphoproliferative response from 735±415 to 4143±1746 cpm. The IFN-g production by cells of candidiasis patients stimulated with Candida albicans antigen was 162±345pg/ml. Candidiasis patients have an impairment in the lymphoproliferative response specific to C. albicans antigen and on IFN-g production and the lymphoproliferative response can be partially restored, in vitro, by IL-10 neutralization

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

Neurological disability in leprosy: incidence and gender association in Sergipe, Brazil

Leprosy remains a public health problem in many countries. The disease affects skin and peripheral nerves and can cause irreversible disabilities. In Brazil, the detection rate of new cases is 18.2/100,000 inhabitants and leprosy control is considered a priority in the state of Sergipe. Studies showing the epidemiological profile and geographical distribution of leprosy cases are needed for effective epidemiological control measures. The objective of this study was to assess the detection rate of new cases, the geographical distribution and association with gender and clinical forms in Sergipe. Data were obtained from the Brazilian Institute of Geography and Statistics and the Information System for Notifiable Diseases. Maps indicating the geographical distribution of leprosy cases and the degree of neurological disabilities of all municipalities of the state were created using Spring, version 5.1.8 and ArcGIS, version 9.3.1. Hyper-endemic leprosy municipalities exist in Sergipe, indicating that the disease remains a major public health problem. The leprosy cases were found to be in municipalities with a higher number of dwellings with nine people per house. A detection rate of 33.0/100,000 inhabitants was noted in 2005, followed by a progressive reduction in the number of new cases until 2010. However, in the same period, an increase of cases with neurological disability was observed. A significant association of males with the multi-bacillary form and neurological disability was observed. This predisposition to severe forms of leprosy in males may be due to a delay in diagnosis and treatment emphasising the need for special attention by the leprosy control programme

Neurological disability in leprosy: incidence and gender association in Sergipe, Brazil

Leprosy remains a public health problem in many countries. The disease affects skin and peripheral nerves and can cause irreversible disabilities. In Brazil, the detection rate of new cases is 18.2/100,000 inhabitants and leprosy control is considered a priority in the state of Sergipe. Studies showing the epidemiological profile and geographical distribution of leprosy cases are needed for effective epidemiological control measures. The objective of this study was to assess the detection rate of new cases, the geographical distribution and association with gender and clinical forms in Sergipe. Data were obtained from the Brazilian Institute of Geography and Statistics and the Information System for Notifiable Diseases. Maps indicating the geographical distribution of leprosy cases and the degree of neurological disabilities of all municipalities of the state were created using Spring, version 5.1.8 and ArcGIS, version 9.3.1. Hyper-endemic leprosy municipalities exist in Sergipe, indicating that the disease remains a major public health problem. The leprosy cases were found to be in municipalities with a higher number of dwellings with nine people per house. A detection rate of 33.0/100,000 inhabitants was noted in 2005, followed by a progressive reduction in the number of new cases until 2010. However, in the same period, an increase of cases with neurological disability was observed. A significant association of males with the multi-bacillary form and neurological disability was observed. This predisposition to severe forms of leprosy in males may be due to a delay in diagnosis and treatment emphasising the need for special attention by the leprosy control programme

CXCR1 and SLC11A1 polymorphisms affect susceptibility to cutaneous leishmaniasis in Brazil: a case-control and family-based study.

BACKGROUND: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice. To look at the interplay between PMN and macrophages in disease progression in humans we asked whether polymorphisms at genes that regulate their infiltration or function are associated with different clinical phenotypes. Specifically, CXCR1 (IL8RA) and CXCR2 (IL8RB) are receptors for chemokines that attract PMN to inflammatory sites. They lie 30-260 kb upstream of SLC11A1, a gene known primarily for its role in regulating macrophage activation, resistance to leishmaniasis, and wound healing responses in mice, but also known to be expressed in PMN, macrophages and dendritic cells. METHODS: Polymorphic variants at CXCR1, CXCR2 and SLC11A1 were analysed using Taqman or ABI fragment separation technologies in cases (60 CL; 60 ML), unrelated controls (n = 120), and multicase families (104 nuclear families; 88 ML, 250 CL cases) from Brazil. Logistic regression analysis, family-based association testing (FBAT) and haplotype analysis (TRANSMIT) were performed. RESULTS: Case-control analysis showed association between the common C allele (OR 2.38; 95% CI 1.23-4.57; P = 0.009) of CXCR1_rs2854386 and CL, supported by family-based (FBAT; Z score 2.002; P = 0.045) analysis (104 nuclear families; 88 ML, 250 CL cases). ML associated with the rarer G allele (Z score 1.999; P = 0.046). CL associated with a 3' insertion/deletion polymorphism at SLC11A1 (Z score 2.549; P = 0.011). CONCLUSIONS: The study supports roles for CXCR1 and SLC11A1 in the outcome of L. braziliensis infection in humans. Slc11a1 does not influence cutaneous lesion development following needle injection of Leishmania in mice, suggesting that its role here might relate to the action of PMN, macrophage and/or dendritic cells in the wound healing response to the sand fly bite. Together with the CXCR1 association, the data are consistent with hypotheses relating to the possible role of PMN in initiation of a lesion following the delivery of parasites via the sand fly bite. Association of ML with the rare derived G allele suggests that PMN also have an important positive role to play in preventing this form of the disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are