Edgar M. Carvalho

Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais

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Lucas P. Carvalho

Universidade Federal da Bahia

Paulo Roberto Lima Machado

Universidade Federal da Bahia

Olı́via Bacellar

Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais

Luiz Henrique Guimarães

Universidade Federal da Bahia

Maria Ilma Araújo

Universidade Federal de Goiás

Albert Schriefer

Universidade Federal da Bahia

Aldina Barral

Fundação Oswaldo Cruz

Phillip Scott

University of Pennsylvania

Amélia Ribeiro de Jesus

Universidade Federal de Sergipe

Luciana Santos Cardoso

Universidade Federal da Bahia

Cooperative Institutions

Universidade Federal da Bahia

459

Complexo Hospitalar Universitário Professor Edgard Santos

304

Fundação Oswaldo Cruz

223

Universidade de São Paulo

130

Hospital Ana Nery

114

Johns Hopkins University

109

Harvard University

107

National Institutes of Health

University of Pennsylvania

Universidade Federal de Minas Gerais

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Paradoxical Coexistence Of Atopic Asthma And Human T-Lymphotropic Virus Type I (HTLV-I) Infection: A Case Report

The Internet Journal of Pulmonary Medicine (2004)

Adelmir Souza‐Machado Álvaro A. Cruz T Sena Galvão André Muniz Aurélia F. Porto

In this case report, the authors report the presence of two supposedly antagonic immune diseases in the same patient. The patient is a 45-year-old white woman with a history of asthma and allergic rhinitis for the last 10 years. Asthmatic symptoms were present and were triggered after exposure to dust and mold. Her Human T-Lymphotropic Virus Type I (HTLV-I) seropositive status was detected by chance five years ago during a routine screening for blood donation. Skin prick tests were positive for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis. Cytokine levels in unstimulated cultures were: IFNgamma= 1195 pg/ ml, TNFalpha = 460 pg/ml, IL5 = 41 pg/ml and IL10 = 265 pg/ml.

Human T-lymphotropic virus

10.5580/464

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Citations (3)

Imunidade humoral e celular em indivíduos curados de leishmaniose visceral

Revista da Sociedade Brasileira de Medicina Tropical (1985)

Roberto Badaró Edgar M. Carvalho Maria de La Glória Orge Orge Rodolfo S. Teixeira Heonir Rocha

Foi realizada avaliação imunológica em 48 indivíduos com históriapregressa de leishmaniose visceral (L. V)eem seis pacientes durante a fase aguda da doença e após o tratamento. Títulos significativos de anticorpos determinados pela técnica de imunofluorescência e/ou ELISA foram observados em 32 (67%) dos 48 casos. A avaliação da resposta imune humoral e celular nos seis pacientes durante a fase ativa da doença demonstrou títulos elevados de anticorpos (média 9536 ± 7169) e resposta línfoproliferativa ausente (323 ± 24). Após o tratamento (3 e 6 meses) os títulos de anticorpos só caíram em três dos seis pacientes, ao passo que linfócitos passaram a responder "in vítro" a antígenos de leíshmânía (11909 ± 5637). Estes dados demonstram que os indivíduos que adquirem leishmaniose visceral não são geneticamente incapacitados de responder a antígeno de leíshmânía equea persistência de títulos elevados de anticorpos anos após o tratamento, sugere que o parasita permaneça no hospedeiro após a cura clínica da doença.

10.1590/s0037-86821985000200003

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Citations (16)

Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis

BMC Infectious Diseases (2013)

Augusto M. Carvalho Andréa Magalhães Lucas P. Carvalho Olı́via Bacellar Phillip Scott

The main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology. Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development. In the present work we investigated the immune response in CL and ML cured individuals. Participants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy. IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA). The frequency of memory CD4+ T cell populations was determined by FACS. Here we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure. In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma. Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST). A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro. This study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo. These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine. Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.

Leishmania braziliensis

10.1186/1471-2334-13-529

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The relationship between atopy and neurological manifestations in HTLV-1 infection

Revista da Sociedade Brasileira de Medicina Tropical (2018)

Raquel Crisóstomo Lima Verde José Abraão Carneiro Neto Silvane Santos Edgar M. Carvalho Marcus Miranda Lessa

Human T-cell lymphotropic virus type 1 (HTLV-1)induces exaggerated Th1 responses, whereas atopy is associated with exacerbated Th2 responses.Here, a cross-sectional study compared the prevalence of atopy in HTLV-1 carriers and HAM/TSP patients. It also compared the spontaneous cytokine production in HTLV-1-infected individuals. A retrospective cohort study evaluated the development of neurological manifestations in atopic and non-atopic carriers.Atopic HAM/TSP patients with high IFN-γ production exhibited higher IL-5 levels than non-atopic patients. Allergic rhinitis accelerated the development of Babinski signals and overactive bladders.Abnormal Th1 and Th2 responses coexist in HTLV-1-infected individuals and allergic diseases may worsen the clinical course of HTLV-1 infections.

Atopy

10.1590/0037-8682-0162-2017

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Immunomodulation of the Allergic Inflammatory Response: New Developments

Inflammation & Allergy - Drug Targets (2010)

Maria Ilma Araújo Régis A. Campos Luciana Santos Cardoso Sérgio C. Oliveira Edgar M. Carvalho

Studies of the molecular mechanisms associated with allergic diseases have lead to a better understanding of the complex processes that underlie their pathogenesis. These mechanisms involve Th2- and Th1-type cells and also some recently described cytokines, such as IL-25 and IL-33. Regulatory mechanisms of allergic inflammation have also been identified. For instance, IL-10, a cytokine produced by many cell types, promotes a decrease in IgE production, and inhibits the release of histamine and other inflammatory mediators by mast cells. Recently, a variety of regulatory cells have been discovered, which, either by direct contact or through the production of IL-10 and/or TGF-β, can inhibit the allergic inflammatory response. IL-10 is produced in high levels by cells of helminth-infected individuals. There is some evidence that such infections protect against the development of allergic diseases. In asthmatic individuals living in endemic areas of schistosomiasis, it has been shown in in vitro studies that there is a modulation of the Th2 response, both by mechanisms involving IL-10, which is produced mainly by monocytes and CD4+CD25+ T regulatory cells, and also by the expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in CD4+ T cells. Studies using parasite antigens to induce the modulation of allergic inflammatory response are being conducted by several groups of researchers and represent new perspectives for the treatment of allergic diseases. Keywords: Asthma, allergy, immunoregulation, atopy

Allergic Inflammation

Allergic response

Pathogenesis

10.2174/187152810791292836

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Failure of Early Treatment of Cutaneous Leishmaniasis in Preventing the Development of an Ulcer

Clinical Infectious Diseases (2002)

Paulo Roberto Lima Machado Cibele Araújo Andrea T. da Silva Roque Pacheco de Almeida Argemiro D’Oliveira

The clinical characteristics and treatment outcome were determined for 26 patients who presented with early-stage cutaneous leishmaniasis. Illness duration ranged from 8 to 20 days, and the commonest clinical presentation was the presence of a papule with small central crust on a lower extremity. Prominent regional adenopathy was found in 22 (85%) of 26 patients. The results of an intradermal skin test for Leishmania were positive for 96% of those patients, and results of serologic testing were positive for 61% of patients tested. Ten (46%) of 22 patients for whom follow-up data were available developed enlargement and ulceration of the lesion despite early antimony therapy and required additional courses of treatment. Histopathological studies of samples from the lesions of 3 patients showed vasculitis. These data show that early therapy for cutaneous leishmaniasis does not prevent the development of an ulcer in one-half of patients. This unfavorable outcome underlines the relevance of local exacerbated inflammatory and immune response in the pathogenesis of the disease.

Papule

10.1086/340526

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Citations (93)

Association of Type 2 Cytokines with Hepatic Fibrosis in HumanSchistosoma mansoniInfection

Infection and Immunity (2004)

Amélia Ribeiro de Jesus Andréa Magalhães Delfin Gonzalez Miranda Roberval Gonzalez Miranda Maria Ilma Araújo

ABSTRACT The objective of this study was to evaluate the role of cytokines in hepatic fibrosis in the prehepatosplenic and early hepatosplenic stages of schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94 patients. Immunological evaluation was performed by the measurement of secreted cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis factor alpha, and transforming growth factor β) in peripheral blood mononuclear cells (PBMC) stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic fibrosis compared to patients with degree I or II fibrosis. Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for 1 year following initial assessment and developed more serious fibrosis during this period. The data suggest a role for type 2 cytokines in hepatic fibrosis in human schistosomiasis mansoni.

Hepatic fibrosis

Schistosoma

10.1128/iai.72.6.3391-3397.2004

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Citations (118)

Seroconversion to Lutzomyia intermedia LinB-13 as a biomarker for developing cutaneous leishmaniasis

Scientific Reports (2017)

Augusto M. Carvalho Kiyoshi F. Fukutani Rohit Sharma Rebecca P. Curvelo José Carlos Miranda

Sand flies inject saliva while feeding in the vertebrate host and anti-saliva antibodies can be used as biomarkers of exposure to Leishmania vectors. We expressed recombinant salivary proteins from Lutzomyia intermedia, a vector of Leishmania braziliensis, and evaluated the seroreactivity in exposed individuals in search for exposure markers. We found a strong correlation among positive serology to recombinant proteins LinB-13, 26, 15, 21 and to salivary proteins: rLinB-13 was the top performing molecule; IgG4 was the most predominant antibody subclass and antibodies to rLinB-13 did not cross react with Lu. longipalpis salivary proteins. By evaluating a cohort of contacts of CL patients, we confirmed that rLinB-13, an antigen 5-related protein, is a marker of exposure to Lu. intermedia with high degree of accuracy. In a 5-year follow up, we determined that individuals who developed CL presented higher anti-rLinB13 IgG responses, before the appearance of clinical symptoms. They also presented a lower frequency of cellular responses to the parasite (DTH). Our results show that seroconversion to a salivary molecule, rLinB-13, is a marker of risk for CL development caused by Leishmania braziliensis. This highlight the possibility of developing tools based on vector molecules to manage the disease in endemic areas.

Seroconversion

Leishmania braziliensis

10.1038/s41598-017-03345-0

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Citations (20)

Unbalanced production of LTB ₄ /PGE ₂ driven by diabetes increases susceptibility to cutaneous leishmaniasis

Emerging Microbes & Infections (2020)

Ícaro Bonyek-Silva Sara Nunes Reinan Lima Santos Filipe Rocha Lima Alexsandro S. Lago

Poorly controlled diabetes mellitus leads to several comorbidities, including susceptibility to infections. Hyperglycemia increases phagocyte responsiveness, however immune cells from people with diabetes show inadequate antimicrobial functions. We and others have shown that aberrant production of leukotriene B4 (LTB4) is detrimental to host defense in models of bacterial infection. Here, we will unveil the consequences of high glucose in the outcome of Leishmania braziliensis skin infection in people with diabetes and determine the role of LTB4 in human phagocytes. We show that diabetes leads to higher systemic levels of LTB4, IL-6 and TNF-α in cutaneous leishmaniasis. Only LTB4 correlated with blood glucose levels and healing time in diabetes comorbidity. Skin lesions of people with leishmaniasis and diabetes exhibit increased neutrophil and amastigote numbers. Monocyte-derived macrophages from these individuals showed higher L. braziliensis loads, reduced production of Reactive Oxygen Species and unbalanced LTB4/PGE2 ratio. Our data reveal a systemic inflammation driven by diabetes comorbidity in opposition to a local reduced capacity to resolve L. braziliensis infection and a worse disease outcome.

10.1080/22221751.2020.1773744

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Citations (14)

Serum markers of rheumatoid arthritis in visceral leishmaniasis: Rheumatoid factor and anti-cyclic citrullinated peptide antibody

Journal of Autoimmunity (2007)

Ajax Mercês Atta Edgar M. Carvalho Selma M. B. Jerônimo Maria Atta

Rheumatoid factor

Isotype

10.1016/j.jaut.2006.12.001

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Citations (43)