88 results on '"Ribeiro‐Dias, F."'
Search Results
2. Protective immune response mediated by neutrophils in experimental visceral leishmaniasis is enhanced by IL-32 gamma
- Author
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Gomes, R.S., Teodoro Silva, Muriel Vilela, Pelli Oliveira, Milton Adriano, Joosten, L.A.B., Ribeiro-Dias, F., Gomes, R.S., Teodoro Silva, Muriel Vilela, Pelli Oliveira, Milton Adriano, Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Item does not contain fulltext
- Published
- 2022
3. The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp
- Author
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Silva, M.V.T., Dos Santos, J.C., Figueiredo, A.M.B., Teufel, L.U., Pereira, J.X., Matos, G.G., Pinto, S.A., Netea, M.G., Gomes, R.S., Joosten, L.A.B., Ribeiro-Dias, F., Silva, M.V.T., Dos Santos, J.C., Figueiredo, A.M.B., Teufel, L.U., Pereira, J.X., Matos, G.G., Pinto, S.A., Netea, M.G., Gomes, R.S., Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Item does not contain fulltext, BACKGROUND: Cells of the innate immune system undergo long-term functional reprogramming in response to Bacillus Calmette-Guérin (BCG) exposure via a process called trained immunity, conferring nonspecific protection to unrelated infections. Here, we investigate whether BCG-induced trained immunity is able to protect against infections caused by different Leishmania spp., protozoa that cause cutaneous and mucosal or visceral lesions. METHODS: We used training models of human monocytes with BCG and subsequent infection by L. braziliensis, L. amazonensis and L. infantum, and the vaccination of wild-type and transgenic mice for IL-32γ before in vivo challenge with parasites. RESULTS: We demonstrated that monocytes trained with BCG presented enhanced ability to kill L. braziliensis, L. amazonensis and L. infantum through increased production of reactive oxygen species. Interleukin (IL)-32 appears to play an essential role in the development of trained immunity. Indeed, BCG exposure induced IL-32 production in human primary monocytes, both mRNA and protein. We have used a human IL-32γ transgenic mouse model (IL-32γTg) to study the effect of BCG vaccination in different Leishmania infection models. BCG vaccination decreased lesion size and parasite load in infections caused by L. braziliensis and reduced the spread of L. amazonensis to other organs in both infected wild-type (WT) and IL-32γTg mice. In addition, BCG reduced the parasite load in the spleen, liver and bone marrow of both WT and IL-32γTg mice infected with L. infantum. BCG vaccination increased inflammatory infiltrate in infected tissues caused by different Leishmania spp. In all infections, the presence of IL-32γ was not mandatory, but it increased the protective and inflammatory effects of BCG-induced training. CONCLUSIONS: BCG's ability to train innate immune cells, providing protection against leishmaniasis, as well as the participation of IL-32γ in this process, pave the way for new treatment strategies
- Published
- 2021
4. Paracoccidioides brasiliensis induces IL-32 and is controlled by IL-15/IL-32/ vitamin D pathway in vitro
- Author
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Matos, Grazzielle Guimaraes de, Barroso de Figueiredo, Ana Marina, Diniz Goncalves, Pedro Hugo, Lima Silva, Lucas Luiz de, Bastista, Aline Carvalho, Borges, Clayton Luiz, Joosten, L.A.B., Ribeiro-Dias, F., Matos, Grazzielle Guimaraes de, Barroso de Figueiredo, Ana Marina, Diniz Goncalves, Pedro Hugo, Lima Silva, Lucas Luiz de, Bastista, Aline Carvalho, Borges, Clayton Luiz, Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Item does not contain fulltext
- Published
- 2021
5. Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis
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Dos Santos, J.C., Leite Quixabeira, Valeria Bernadete, Teodoro Silva, Muriel Vilela, Damen, M.S.M.A., Schraa, K., Jaeger, M., Oosting, M., Keating, S.T., Netea, M.G., Ribeiro-Dias, F., Joosten, L.A., Dos Santos, J.C., Leite Quixabeira, Valeria Bernadete, Teodoro Silva, Muriel Vilela, Damen, M.S.M.A., Schraa, K., Jaeger, M., Oosting, M., Keating, S.T., Netea, M.G., Ribeiro-Dias, F., and Joosten, L.A.
- Abstract
Contains fulltext : 217639.pdf (publisher's version ) (Open Access)
- Published
- 2020
6. IL-15 enhances the capacity of primary human macrophages to control Leishmania braziliensis infection by IL-32/vitamin D dependent and independent pathways
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Lima Silva, Lucas Luiz de, Gomes, R.S., Teodoro Silva, Muriel Vilela, Joosten, L.A.B., Ribeiro-Dias, F., Lima Silva, Lucas Luiz de, Gomes, R.S., Teodoro Silva, Muriel Vilela, Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Item does not contain fulltext
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- 2020
7. beta-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32
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Dos Santos, J.C., Barroso de Figueiredo, Ana Marina, Teodoro Silva, Muriel Vilela, Cirovic, Branko, Bree, L.C.J. de, Damen, M.S.M.A., Moorlag, S.J.C.F.M., Helsen, M.M.A., Oosting, M., Keating, S.T., Netea, M.G., Ribeiro-Dias, F., Joosten, L.A.B., Dos Santos, J.C., Barroso de Figueiredo, Ana Marina, Teodoro Silva, Muriel Vilela, Cirovic, Branko, Bree, L.C.J. de, Damen, M.S.M.A., Moorlag, S.J.C.F.M., Helsen, M.M.A., Oosting, M., Keating, S.T., Netea, M.G., Ribeiro-Dias, F., and Joosten, L.A.B.
- Abstract
Contains fulltext : 207901.pdf (publisher's version ) (Open Access)
- Published
- 2019
8. The role of interleukin-32 in infections caused by New World Leishmania species and identification of novel treatment strategies
- Author
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Joosten, L.A.B., Ribeiro Dias, F., Dos Santos, J.C., Joosten, L.A.B., Ribeiro Dias, F., and Dos Santos, J.C.
- Abstract
Radboud University, 28 februari 2019, Promotores : Joosten, L.A.B., Ribeiro Dias, F., Contains fulltext : 200683.pdf (publisher's version ) (Open Access)
- Published
- 2019
9. Human Interleukin-32 gamma Plays a Protective Role in an Experimental Model of Visceral Leishmaniasis in Mice
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Gomes, R.S., Teodoro Silva, Muriel Vilela, Dos Santos, J.C., Linge, Christine van, Reis, Juliana Machado, Teixeira, M.M., Dinarello, C.A., Joosten, L.A.B., Ribeiro-Dias, F., Gomes, R.S., Teodoro Silva, Muriel Vilela, Dos Santos, J.C., Linge, Christine van, Reis, Juliana Machado, Teixeira, M.M., Dinarello, C.A., Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Contains fulltext : 191165.pdf (publisher's version ) (Closed access)
- Published
- 2018
10. Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex
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Herkert, P.F., Dos Santos, J.C., Hagen, F., Ribeiro-Dias, F., Queiroz-Telles, F., Netea, M.G., Meis, J.F., Joosten, L.A.B., Herkert, P.F., Dos Santos, J.C., Hagen, F., Ribeiro-Dias, F., Queiroz-Telles, F., Netea, M.G., Meis, J.F., and Joosten, L.A.B.
- Abstract
Contains fulltext : 190812.pdf (publisher's version ) (Closed access), Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations. Cryptococcus gattii sensu stricto and C. deuterogattii affect mainly immunocompetent hosts; however, C. bacillisporus, C. decagattii, and C. tetragattii cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the C. gattii species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs). Cryptococcus bacillisporus and C. deuterogattii induced the lowest levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 among the five species of the C. gattii complex. Cryptococcus deuterogattii induced higher levels of IL-22 than those induced by C. tetragattii and the environmental species C. flavescens In addition, C. bacillisporus and C. gattii sensu stricto proliferated inside human monocyte-derived macrophages after 24 h of infection. All Cryptococcus species were able to generate reactive oxygen species (ROS) in human PBMCs, with C. bacillisporus and C. deuterogattii being more efficient than the other species. In conclusion, C. bacillisporus and C. deuterogattii induce lower levels of the proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 and higher ROS levels than those induced by the other species. Species of the Cryptococcus gattii complex have different abilities to induce cytokine and ROS production by human PBMCs.
- Published
- 2018
11. IL-32gamma promotes the healing of murine cutaneous lesions caused by Leishmania braziliensis infection in contrast to Leishmania amazonensis
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Gomes, R.S., Silva, M.V.T., Santos, J.C. Dos, Silva, L.L. de Lima, Batista, A.C., Machado, J.R., Teixeira, M.M., Dorta, M.L., Oliveira, M.A. de, Dinarello, C.A., Joosten, L.A.B., Ribeiro-Dias, F., Gomes, R.S., Silva, M.V.T., Santos, J.C. Dos, Silva, L.L. de Lima, Batista, A.C., Machado, J.R., Teixeira, M.M., Dorta, M.L., Oliveira, M.A. de, Dinarello, C.A., Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Contains fulltext : 177364.pdf (publisher's version ) (Open Access), BACKGROUND: Interleukin 32 (IL-32) is a pro-inflammatory cytokine induced in patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. Here, we investigated whether IL-32 is also expressed in patient lesions caused by L. amazonensis. In addition, we evaluated experimental L. amazonensis and L. braziliensis infections in C57BL/6 transgenic mice for human IL-32gamma (IL-32gammaTg) in comparison with wild-type (WT) mice that do not express the IL-32 gene. RESULTS: Human cutaneous lesions caused by L. amazonensis express higher levels of IL-32 than healthy control skin. In mice, the presence of IL-32gamma promoted the control of cutaneous lesions caused by L. braziliensis, but not lesions caused by L. amazonensis in an ear dermis infection model. In addition, IL-32gammaTg mice displayed less tissue parasitism and inflammation in IL-32gammaTg than WT mice during the healing phase of L. braziliensis infection. Production of antigen-specific pro-inflammatory cytokines was higher in IL-32gammaTg mice than in WT mice during L. braziliensis infection but not during L. amazonensis infection. CONCLUSIONS: Human cutaneous lesions caused by L. amazonensis express high levels of IL-32. In mice, the presence of IL-32gamma contributes to the lesion healing caused by L. braziliensis but not by L. amazonensis. Data suggest that despite the ability for both species to induce IL-32 in humans, the connections between this cytokine and other immune players induced by related species of parasites can lead to distinct outcomes of the murine infections.
- Published
- 2017
12. Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
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Santos, J.C. Dos, Heinhuis, B., Gomes, R.S., Damen, M.S.M.A., Real, F., Mortara, R.A., Keating, S.T., Dinarello, C.A., Joosten, L.A.B., Ribeiro-Dias, F., Santos, J.C. Dos, Heinhuis, B., Gomes, R.S., Damen, M.S.M.A., Real, F., Mortara, R.A., Keating, S.T., Dinarello, C.A., Joosten, L.A.B., and Ribeiro-Dias, F.
- Abstract
Contains fulltext : 169942.pdf (publisher's version ) (Open Access), BACKGROUND: Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32gamma, and show that intracellular IL-32gamma protein production is dependent on endogenous TNFalpha. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFalpha and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and beta-defensin 2 production regulated by IL-32. CONCLUSIONS: Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.
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- 2017
13. The NOD2 receptor is crucial for immune responses towards New World Leishmania species
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Dos Santos, J.C., Damen, M.S.M.A., Oosting, M., Jong, D.J. de, Heinhuis, B., Gomes, R.S., Netea, M.G., Ribeiro-Dias, F., Joosten, L.A.B., Dos Santos, J.C., Damen, M.S.M.A., Oosting, M., Jong, D.J. de, Heinhuis, B., Gomes, R.S., Netea, M.G., Ribeiro-Dias, F., and Joosten, L.A.B.
- Abstract
Contains fulltext : 179623.pdf (publisher's version ) (Open Access)
- Published
- 2017
14. Interleukin 32: a novel player in the control of infectious diseases
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Ribeiro-Dias, F., Gomes, R., Silva, L.L. de Lima, Santos, J.C. Dos, Joosten, L.A.B., Ribeiro-Dias, F., Gomes, R., Silva, L.L. de Lima, Santos, J.C. Dos, and Joosten, L.A.B.
- Abstract
Contains fulltext : 169721.pdf (publisher's version ) (Closed access), Interleukin 32 (IL-32) is a proinflammatory cytokine, expressed as 9 distinct isoforms. The most active isoform is the predominantly intracellular-functioning IL-32gamma. Involvement of IL-32 in infectious diseases is increasingly being appreciated. Production of IL-32 promotes pathways that serve to control bacterial infection, especially those caused by mycobacteria. A similar role for this cytokine is observed in the cellular response to viral infections. In addition to its protective effects against microorganisms, IL-32 is involved in immunopathogenesis of some infectious diseases. In parasitic diseases, it has been demonstrated that this cytokine is induced by Leishmania infection. In this review, we summarize the present data on the role of IL-32 in infectious diseases, highlighting this cytokine as new target for control of infections.
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- 2017
15. Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFalpha and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner
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Galdino, H., Jr., Gomes, R., Santos, J.C. Dos, Pessoni, L.L., Maldaner, A.E., Marques, S.M., Gomes, C.M., Dorta, M.L., Oliveira, M.A. de, Joosten, L.A., Ribeiro-Dias, F., Galdino, H., Jr., Gomes, R., Santos, J.C. Dos, Pessoni, L.L., Maldaner, A.E., Marques, S.M., Gomes, C.M., Dorta, M.L., Oliveira, M.A. de, Joosten, L.A., and Ribeiro-Dias, F.
- Abstract
Contains fulltext : 170874.pdf (publisher's version ) (Closed access), While the role of Toll-like receptors (TLRs) has been investigated in murine models of tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis, the interaction between TLRs and Leishmania sp. has not been investigated in human cells. The aim of this study was to evaluate the involvement of TLR4 in cytokine production of human peripheral blood mononuclear cells (PBMCs) induced by L. braziliensis, and whether the parasite alters the expression of TLR4 on monocytes/macrophages. Amastigote forms were obtained from mice lesions and PBMCs were isolated from healthy donors. PBMCs were cultured in absence or presence of IFNgamma, TLR4 neutralizing antibodies, natural antagonist of TLR4 (Bartonella LPS), TLR4 agonist (E. coli LPS), and amastigote forms. The concentrations of tumor necrosis factor (TNFalpha) and interleukin 10 (IL-10) were assayed by ELISA and TLR4 expression by flow cytometry. Amastigotes forms of L. braziliensis induced TNFalpha and IL-10 production only in IFNgamma-primed PBMCs. The TNFalpha and IL-10 production was inhibited by TLR4 neutralization, both with anti-TLR4 antibodies and Bartonella LPS. Interestingly, addition of E. coli LPS further increased TNFalpha but not IL-10 production induced by L. braziliensis amastigotes. Amastigotes of L. braziliensis strongly reduced membrane TLR4 expression on monocytes/macrophages, apparently by internalization after the infection. The present study reveals that TLR4 drives the production of TNFalpha and IL-10 induced by L. braziliensis amastigotes and that the parasites decrease TLR4 expression on monocyte surface.
- Published
- 2016
16. The role of interleukin-32 in infections caused by New World Leishmania species and identification of novel treatment strategies
- Author
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Dos Santos, J.C., Joosten, L.A.B., Ribeiro Dias, F., and Radboud University Nijmegen
- Subjects
Radboud Institute for Molecular Life Sciences ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,lnfectious Diseases and Global Health [Radboudumc 4] - Abstract
Contains fulltext : 200683.pdf (Publisher’s version ) (Open Access) Radboud University, 28 februari 2019 Promotores : Joosten, L.A.B., Ribeiro Dias, F.
- Published
- 2019
17. Leishmania braziliensis enhances monocyte responses to promote anti-tumor activity.
- Author
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Dos Santos JC, Moreno M, Teufel LU, Chilibroste S, Keating ST, Groh L, Domínguez-Andrés J, Williams DL, Ma Z, Lowman DW, Ensley HE, Novakovic B, Ribeiro-Dias F, Netea MG, Chabalgoity JA, and Joosten LAB
- Subjects
- Humans, Mice, Animals, Monocytes, Leishmania braziliensis, Neoplasms, Leishmaniasis, Cutaneous
- Abstract
Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensis develop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensis is mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensis exerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitro and identifies its potential for cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
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18. The influence of a copper efflux pump in Histoplasma capsulatum virulence.
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Moraes D, Tristão GB, Rappleye CA, Ray SC, Ribeiro-Dias F, Gomes RS, Assunção LDP, Paccez JD, Zancopé-Oliveira RM, Silva-Bailão MG, Soares CMA, and Bailão AM
- Subjects
- Animals, Mice, Virulence, Macrophages metabolism, Immunity, Innate, Histoplasma genetics, Copper metabolism
- Abstract
During the infectious process, pathogenic microorganisms must obtain nutrients from the host in order to survive and proliferate. These nutritional sources include the metallic nutrient copper. Despite its essentiality, copper in large amounts is toxic. Host defense mechanisms use high copper poisoning as a fungicidal strategy to control infection. Transcriptional analyses showed that yeast cultured in the presence of copper or inside macrophages (24 h) had elevated expression of CRP1, a copper efflux pump, suggesting that Histoplasma capsulatum could be exposed to a high copper environment in macrophages during the innate immune stage of infection. Accordingly, macrophages cultured in high copper are more efficient in controlling H. capsulatum growth. Also, silencing of ATP7a, a copper pump that promotes the copper influx in phagosomes, increases fungal survival in macrophages. The rich copper environment faced by the fungus is not dependent on IFN-γ, since fungal CRP1 expression is induced in untreated macrophages. Appropriately, CRP1 knockdown fungal strains are more susceptible to macrophage control than wild-type yeasts. Additionally, CRP1 silencing decreases fungal burden in mice during the phase of innate immune response (4-day postinfection) and CRP1 is required for full virulence in a macrophage cell lines (J774 A.1 and RAW 264.7), as well as primary cells (BMDM). Thus, induction of fungal copper detoxifying genes during innate immunity and the attenuated virulence of CRP1-knockdown yeasts suggest that H. capsulatum is exposed to a copper-rich environment at early infection, but circumvents this condition to establish infection., (© 2023 Federation of European Biochemical Societies.)
- Published
- 2024
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19. Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis .
- Author
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de Figueiredo AMB, Moraes D, Bailão AM, Rocha OB, Silva LOS, Ribeiro-Dias F, and Soares CMA
- Subjects
- Humans, Proteome metabolism, Saccharomyces cerevisiae, Proteomics, Macrophages microbiology, Paracoccidioides
- Abstract
Paracoccidioides spp. is the etiologic agent of Paracoccidioidomycosis (PCM), a systemic disease with wide distribution in Latin America. Macrophages are very important cells during the response to infection by P. brasiliensis . In this study, we performed a proteomic analysis to evaluate the consequences of P. brasiliensis yeast cells on the human THP-1 macrophage proteome. We have identified 443 and 2247 upregulated or downregulated proteins, respectively, in macrophages co-cultured with yeast cells of P. brasiliensis in comparison to control macrophages unexposed to the fungus. Proteomic analysis revealed that interaction with P. brasiliensis caused metabolic changes in macrophages that drastically affected energy production pathways. In addition, these macrophages presented regulated many factors related to epigenetic modifications and gene transcription as well as a decrease of many proteins associated to the immune system activity. This is the first human macrophage proteome derived from interactions with P. brasiliensis , which contributes to elucidating the changes that occur during the host response to this fungus. Furthermore, it highlights proteins that may be targets for the development of new therapeutic approaches to PCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Figueiredo, Moraes, Bailão, Rocha, Silva, Ribeiro-Dias and Soares.)
- Published
- 2023
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20. Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics.
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Inácio MM, Moreira ALE, Cruz-Leite VRM, Mattos K, Silva LOS, Venturini J, Ruiz OH, Ribeiro-Dias F, Weber SS, Soares CMA, and Borges CL
- Abstract
Fungal infections represent a serious global health problem, causing damage to health and the economy on the scale of millions. Although vaccines are the most effective therapeutic approach used to combat infectious agents, at the moment, no fungal vaccine has been approved for use in humans. However, the scientific community has been working hard to overcome this challenge. In this sense, we aim to describe here an update on the development of fungal vaccines and the progress of methodological and experimental immunotherapies against fungal infections. In addition, advances in immunoinformatic tools are described as an important aid by which to overcome the difficulty of achieving success in fungal vaccine development. In silico approaches are great options for the most important and difficult questions regarding the attainment of an efficient fungal vaccine. Here, we suggest how bioinformatic tools could contribute, considering the main challenges, to an effective fungal vaccine.
- Published
- 2023
- Full Text
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21. Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis -Induction of Cytokine Production in Peripheral Blood Mononuclear Cells.
- Author
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de Figueiredo AMB, Dos Santos JC, Kischkel B, Ardiansyah E, Oosting M, Guimarães Matos G, Barreto Neves Oliveira I, van de Veerdonk F, Netea MG, Soares CMA, Ribeiro-Dias F, and Joosten LAB
- Abstract
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides and the different clinical forms of the disease are associated with the host immune responses. Quantitative trait loci mapping analysis was performed to assess genetic variants associated with mononuclear-cells-derived cytokines induced by P. brasiliensis on 158 individuals. We identified the rs11053595 SNP, which is present in the CLEC7A gene (encodes the Dectin-1 receptor) and the rs62290169 SNP located in the PROM1 gene (encodes CD133) associated with the production of IL-1β and IL-22, respectively. Functionally, the blockade of the dectin-1 receptor abolished the IL-1β production in P. brasiliensis- stimulated PBMCs. Moreover, the rs62290169-GG genotype was associated with higher frequency of CD38
+ Th1 cells in PBMCs cultured with P. brasiliensis yeasts. Therefore, our research indicates that the CLEC7A and PROM1 genes are important for the cytokine response induced by P. brasiliensis and may influence the Paracoccidioidomycosis disease outcome.- Published
- 2023
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22. Single nucleotide polymorphisms in genes involved in immune responses and outcome of tegumentary leishmaniasis.
- Author
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Oliveira IBN, Borges CL, Gomes RS, and Ribeiro-Dias F
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- Animals, Immunity, Neglected Diseases, Polymorphism, Single Nucleotide, Leishmania genetics, Leishmaniasis parasitology, Leishmaniasis, Cutaneous epidemiology, Psychodidae genetics, Psychodidae parasitology
- Abstract
Leishmaniases are neglected tropical diseases with a broad clinical spectrum. Tegumentary leishmaniasis (TL) is a disease caused by different Leishmania species, transmitted by phlebotomine sand flies and distributed worldwide. TL can present a cutaneous (CL) or mucocutaneous (MCL) clinical form depending on factors inherent to the parasite, the host and the vector. Polymorphisms in the immune response genes are host genetic factors that influence the pathogenesis or control of leishmaniasis. Single nucleotide polymorphisms (SNPs) in immune genes have been evaluated in several countries where leishmaniasis is endemic. In this review, we report studies on SNPs in several immune genes that might be associated with susceptibility or resistance to TL. We summarize studies from around the world and in Brazil, highlight the difficulties of these studies and future analyses needed to enhance our knowledge regarding host genetic factors in TL. Understanding the genetic characteristics of the host that facilitate resistance or susceptibility to leishmaniasis can contribute to the development of immunotherapy schedules for this disease. The current treatment methods are toxic, and no human vaccine is available., Competing Interests: Declaration of Competing Interest The authors state no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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23. Detection of SARS-CoV-2 virus via dynamic light scattering using antibody-gold nanoparticle bioconjugates against viral spike protein.
- Author
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Silva PBD, Silva JRD, Rodrigues MC, Vieira JA, Andrade IA, Nagata T, Santos AS, Silva SWD, Rocha MCOD, Báo SN, Moraes-Vieira PM, Proença-Modena J, Angelim MKC, de Souza GF, Muraro SP, de Barros ALB, de Souza Martins GA, Ribeiro-Dias F, Machado G, Fessel MR, Chudzinski-Tavassi AM, Ronconi CM, Gonçalves D, Curi R, Oliveira ON, and Azevedo RB
- Subjects
- COVID-19 Testing, Dynamic Light Scattering, Gold chemistry, Humans, Immunoassay methods, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Viral Proteins, Biosensing Techniques methods, COVID-19 diagnosis, Metal Nanoparticles chemistry
- Abstract
Mass testing for the diagnosis of COVID-19 has been hampered in many countries owing to the high cost of genetic material detection. This study reports on a low-cost immunoassay for detecting SARS-CoV-2 within 30 min using dynamic light scattering (DLS). The immunosensor comprises 50-nm gold nanoparticles (AuNPs) functionalized with antibodies against SARS-CoV-2 spike glycoprotein, whose bioconjugation was confirmed using transmission electron microscopy (TEM), UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and surface-enhanced Raman scattering spectroscopy (SERS). The specific binding of the bioconjugates to the spike protein led to an increase in bioconjugate size, with a limit of detection (LOD) 5.29 × 10
3 TCID50 /mL (Tissue Culture Infectious Dose). The immunosensor was also proven to be selective upon interaction with influenza viruses once no increase in size was observed after DLS measurement. The strategy proposed here aimed to use antibodies conjugated to AuNPs as a generic platform that can be extended to other detection principles, enabling technologies for low-cost mass testing for COVID-19., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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24. Lipophosphoglycan From Dermotropic New World Leishmania Upregulates Interleukin-32 and Proinflammatory Cytokines Through TLR4 and NOD2 Receptors.
- Author
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Silveira MB, Gomes RS, Shio MT, Rugani JN, Paranaiba LF, Soares RP, and Ribeiro-Dias F
- Subjects
- Cytokines metabolism, Escherichia coli genetics, Glycosphingolipids, Humans, Interleukin-6 metabolism, Interleukins metabolism, Leukocytes, Mononuclear metabolism, Lipopolysaccharides, Nod2 Signaling Adaptor Protein metabolism, RNA, Messenger, Toll-Like Receptor 4 metabolism, Leishmania, Leishmaniasis
- Abstract
Interleukin-32 (IL-32) is produced during Leishmania infection, but the components of the parasite that induce its production are unknown. An important multivirulence factor of Leishmania spp. protozoa is the lipophosphoglycan (LPG), which plays a crucial role in the host-parasite interaction. Here, the ability of LPGs from two dermotropic Leishmania species to induce IL-32 production was evaluated in human peripheral blood mononuclear cells (PBMCs). Additionally, the potential receptors involved in this activation were assessed. PBMCs from healthy individuals were stimulated with LPGs from L. amazonensis (La) or L. braziliensis (Lb), live promastigotes of La or Lb and E. coli lipopolysaccharide (LPS, TLR4 agonist) as control. Blockers of TLR4 ( Bartonella quintana LPS or monoclonal antibody) and Ponatinib (RIPK2 inhibitor, NOD2 pathway) were used to evaluate the receptors. ELISA was performed for IL-32 expression and cytokine (IL-1β and IL-6) production in cell lysates and in supernatants, respectively. Expression of TLR4 (2 h, 24 h) was assessed by flow cytometry. IL-32γ mRNA transcript was analyzed by qPCR. It was observed that LPG from Leishmania , like whole parasites, induced the production of IL-32, IL-1β and IL-6. Both LPGs induced the expression of IL32 γ mRNA. The production of IL-32 was earlier detected (6 h) and positively associated with the production of IL-1β and IL-6. The induction of cytokines (IL-32, IL-1β and IL-6) was dependent on TLR4 and NOD2. The TLR4 was internalized after interaction with LPG. Therefore, our data suggest that LPGs from La and Lb are components of Leishmania able to upregulate IL-32 and other pro-inflammatory cytokines in a TLR4- and NOD2-dependent manner. In addition, LPG-induced IL-32 seems to be necessary for IL-1β and IL-6 production. To identify the parasite factors and host receptors involved in IL-32 induction is crucial to reveal potential targets for novel strategies to control leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silveira, Gomes, Shio, Rugani, Paranaiba, Soares and Ribeiro-Dias.)
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- 2022
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25. A Critical Overview of Interleukin 32 in Leishmaniases.
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Ribeiro-Dias F and Oliveira IBN
- Subjects
- Animals, Cytokines metabolism, Humans, Interleukins metabolism, Mice, Leishmania metabolism, Leishmaniasis, Cutaneous, Leishmaniasis, Visceral
- Abstract
Interleukin-32 (IL-32) has several immune regulatory properties, which have driven its investigation in the context of various diseases. IL-32 expression is reported to be induced in the lesions of patients with American tegumentary leishmaniasis (ATL) by the New World Leishmania spp. that are responsible for causing ATL and visceral leishmaniasis (VL). IL-32 expression may elevate the inflammatory process through the induction of pro-inflammatory cytokines and also via mechanisms directed to kill the parasites. The genetic variants of IL-32 might be associated with the resistance or susceptibility to ATL, while different isoforms of IL-32 could be associated with distinct T helper lymphocyte profiles. IL-32 also determines the transcriptional profile in the bone marrow progenitor cells to mediate the trained immunity induced by β-glucan and BCG, thereby contributing to the resistance against Leishmania . IL-32γ is essential for the vitamin D-dependent microbicidal pathway for parasite control. In this context, the present review report briefly discusses the data retrieved from the studies conducted on IL-32 in leishmaniasis in humans and mice to highlight the current challenges to understanding the role of IL-32 in leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ribeiro-Dias and Oliveira.)
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- 2022
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26. Interleukin-32 γ in the Control of Acute Experimental Chagas Disease.
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Braga YLL, Neto JRC, Costa AWF, Silva MVT, Silva MV, Celes MRN, Oliveira MAP, Joosten LAB, Ribeiro-Dias F, Gomes RS, and Machado JR
- Subjects
- Animals, Humans, Male, Mice, Acute Disease, Chagas Cardiomyopathy, Mice, Inbred C57BL, Mice, Transgenic, Models, Animal, Chagas Disease immunology, Inflammation genetics, Inflammation metabolism, Interleukins genetics, Interleukins metabolism, Myocardium pathology, Parasitemia immunology, Trypanosoma cruzi physiology
- Abstract
Chagas disease (CD) is an important parasitic disease caused by Trypanosoma cruzi . Interleukin-32 (IL-32) plays an important role in inflammation and in the development of Th1/Th17 acquired immune responses. We evaluated the influence of IL-32 γ on the immune response profile, pathogenesis of myocarditis in acute experimental CD, and control of the disease. For this, C57BL/6 wild-type (WT) and IL-32 γ Tg mice were infected subcutaneously with 1,000 forms of Colombian strain of T. cruzi . In the histopathological analyzes, T. cruzi nests, myocarditis, and collagen were quantified in cardiac tissue. Cytokine productions (IL-32, IFN- γ , TNF- α , IL-10, and IL-17) were measured in cardiac homogenate by ELISA. The IL-32 γ Tg mice showed a better control of parasitemia and T. cruzi nests in the heart than WT mice. Infected-WT and -IL-32 γ Tg mice showed similar levels of IFN- γ , TNF- α , and IL-17, but IL-10 was significantly higher expressed in IL-32 γ Tg than in WT mice. The cytokine profile found in IL-32 γ Tg animals contributed to body weight maintenance, parasitemia control, and survival. Our results indicate that the presence of human IL-32 γ in mice infected with the Colombian strain of T. cruzi is important for infection control during the acute phase of Chagas disease., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this review article. FR-D is CNPq research's fellow. RSG, MAPO, and F-RD are members of the INCT-IPH (National Institute of Science and Technology for the strategies in host-pathogen interaction, grant of Fundação de amparo à pesquisa do estado de Goiás, FAPEG)., (Copyright © 2022 Yarlla L. L. Braga et al.)
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- 2022
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27. Protective immune response mediated by neutrophils in experimental visceral leishmaniasis is enhanced by IL-32γ.
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Gomes RS, Silva MVT, Oliveira MAP, Joosten LAB, and Ribeiro-Dias F
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- Animals, Interleukins genetics, Liver cytology, Liver immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neutrophil Infiltration immunology, Phagocytosis immunology, Protein Isoforms genetics, Reactive Oxygen Species metabolism, Spleen cytology, Spleen immunology, Interleukins immunology, Leishmania infantum immunology, Leishmaniasis, Visceral immunology, Neutrophils immunology, Th17 Cells immunology
- Abstract
Neutrophils are important cells in protection against microbial infections including visceral leishmaniasis (VL). It is well known that IL-32γ increases the protective T helper 17 cell mediated immune response against Leishmania infantum. Thus, in this study we evaluated whether IL-32 γ can increase the protective role of neutrophils against VL. In comparison with wild type (WT) mice, transgenic mice for human IL-32 γ (IL-32 γ Tg) presented a higher frequency and absolute number of neutrophils in both spleen and liver after the establishment of L. infantum infection. The IL-32 concentrations correlated with neutrophil numbers in the infected tissues. The IL-32 γ -induced recruitment of neutrophils was dependent on IL-17, since inhibition of Th17 T cells generation and IL-17 production with digoxin treatment reversed the effects of IL-32 γ. In murine neutrophils, the presence of IL-32 γ enhanced the phagocytosis of L. infantum via CR3. In addition, murine IL-32 γ Tg neutrophils were able to kill L. infantum due to the increased production of ROS when compared with WT neutrophils. In fact, IL-32 γ Tg mice lost their ability to control infection by L. infantum when neutrophils were depleted. In parallel, treatment of human neutrophils with recombinant IL-32 γ increased phagocytosis and ROS-dependent killing of L. infantum, similarly to murine IL-32 γ Tg neutrophils. The data show that IL-32 γ induces neutrophil recruitment to organs affected by VL and increases phagocytosis and killing of L. infantum by neutrophils. Together, data indicate the pivotal axis IL-32 γ -Th17-neutrophils to control VL., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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28. New world Leishmania spp. infection in people living with HIV: Concerns about relapses and secondary prophylaxis.
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Araújo CF, Oliveira IBN, Silva MVT, Pereira LIA, Pinto SA, Silveira MB, Dorta ML, Fonseca SG, Gomes RS, and Ribeiro-Dias F
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- CD8-Positive T-Lymphocytes, Humans, Recurrence, Coinfection, HIV Infections complications, HIV Infections drug therapy, Leishmania, Leishmaniasis, Leishmaniasis, Visceral
- Abstract
Coinfection with the human immunodeficiency virus (HIV) and Leishmania impairs immune responses, increases treatment failure and relapse rates in patients with American tegumentary leishmaniasis (ATL), as well as visceral leishmaniasis (VL). There is insufficient data on the treatment, relapse, and secondary prophylaxis in patients coinfected with HIV/Leishmania in Brazil. This study investigated patients with HIV/ATL and HIV/VL to describe the outcome of leishmaniasis in patients assisted at a referral hospital of Brazilian midwestern region. Patients with HIV/ATL (n = 21) mainly presented cutaneous diseases (76.2%) with an overall relapse rate of 28.57% after treatment, whereas HIV/VL (n = 28) patients accounted for 17.5% of the cases. The counts of CD4
+ T cells and CD8+ T cells and the CD4+ /CD8+ cell ratios at diagnosis or relapses were not significantly different between relapsing and non-relapsing patients. Patients with HIV/ATL or HIV/VL showed high levels of activation markers in CD4+ and CD8+ T cells. The regular use of highly active antiretroviral therapy (HAART) and viral load at the time of diagnosis did not influence the relapse rates. Relapses occurred in 36.4% (4/11) of the patients with HIV/VL receiving secondary prophylaxis and in 5.9% (1/17) of the patients who did not receive secondary prophylaxis (p = 0.06). These data are relevant for the therapeutic management of the patients coinfected with HIV/Leishmania., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
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29. Toll-like receptor 10 controls TLR2-induced cytokine production in monocytes from patients with Parkinson's disease.
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da Rocha Sobrinho HM, Saar Gomes R, da Silva DJ, Quixabeira VBL, Joosten LAB, Ribeiro de Barros Cardoso C, and Ribeiro-Dias F
- Subjects
- Adult, Aged, Cells, Cultured, Female, Humans, Leukocytes, Mononuclear metabolism, Male, Middle Aged, Parkinson Disease diagnosis, Prospective Studies, Cytokines blood, Monocytes metabolism, Parkinson Disease blood, Toll-Like Receptor 10 blood, Toll-Like Receptor 2 blood
- Abstract
Peripheral inflammation, particularly mediated by monocytes, can cause neuroinflammation in Parkinson's disease (PD). We investigated the mechanism of TLR2-induced cytokine impairment in peripheral monocytes from PD patients and the association between the presence of CD14
+ TLR10+ monocytes and PD severity. Peripheral blood mononuclear cells from PD patients and healthy individuals were evaluated for TLR expression on monocyte subsets (CD14 and CD16 expression) using flow cytometry. Moreover, cytokines were evaluated using flow cytometry after stimulation with Pam3 Cys (TLR2/TLR1 agonist) in the absence or presence of neutralizing antibodies to TLR10. The severity of PD was assessed using the unified PD rating scale (UPDRS) and motor activity, anxiety (BAI), depression (BDI), and fatigue (PD Fatigue Scale-16) scales. The frequency of CD14+ TLR10+ monocytes and expression intensity of TLR2 and TLR10 were higher in patients with PD than healthy individuals. The frequency of intermediate monocytes (CD14++ CD16+ ) was not significantly increased in patients with PD, but was the main monocyte subset expressing TLR10. The TLR2/TLR1-impaired cytokine production (IL-6, TNFα, IL-8, and IL-10) in PD patients was reversed by neutralizing TLR10. The high frequency of total CD14+ TLR10+ monocytes was associated with a reduction in the severity of PD according to the evaluation of motor and nonmotor symptoms. Peripheral monocytes from patients with PD showed phenotypic and functional alterations. The expression of TLR10 on monocytes can protect against PD by controlling TLR2-induced cytokine production. Furthermore, data suggested that a low frequency of CD14+ TLR10+ monocytes indicates the severity of PD. The results identified new opportunities for the development of novel PD neuroprotective therapies., (© 2021 Wiley Periodicals LLC.)- Published
- 2021
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30. The role of IL-32 in Bacillus Calmette-Guérin (BCG)-induced trained immunity in infections caused by different Leishmania spp.
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Silva MVT, Dos Santos JC, Figueiredo AMB, Teufel LU, Pereira JX, Matos GG, Pinto SA, Netea MG, Gomes RS, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Animals, Mice, Mice, Inbred BALB C, Mice, Transgenic, BCG Vaccine, Interleukins immunology, Leishmania, Leishmaniasis immunology, Mycobacterium bovis
- Abstract
Background: Cells of the innate immune system undergo long-term functional reprogramming in response to Bacillus Calmette-Guérin (BCG) exposure via a process called trained immunity, conferring nonspecific protection to unrelated infections. Here, we investigate whether BCG-induced trained immunity is able to protect against infections caused by different Leishmania spp., protozoa that cause cutaneous and mucosal or visceral lesions., Methods: We used training models of human monocytes with BCG and subsequent infection by L. braziliensis, L. amazonensis and L. infantum, and the vaccination of wild-type and transgenic mice for IL-32γ before in vivo challenge with parasites., Results: We demonstrated that monocytes trained with BCG presented enhanced ability to kill L. braziliensis, L. amazonensis and L. infantum through increased production of reactive oxygen species. Interleukin (IL)-32 appears to play an essential role in the development of trained immunity. Indeed, BCG exposure induced IL-32 production in human primary monocytes, both mRNA and protein. We have used a human IL-32γ transgenic mouse model (IL-32γTg) to study the effect of BCG vaccination in different Leishmania infection models. BCG vaccination decreased lesion size and parasite load in infections caused by L. braziliensis and reduced the spread of L. amazonensis to other organs in both infected wild-type (WT) and IL-32γTg mice. In addition, BCG reduced the parasite load in the spleen, liver and bone marrow of both WT and IL-32γTg mice infected with L. infantum. BCG vaccination increased inflammatory infiltrate in infected tissues caused by different Leishmania spp. In all infections, the presence of IL-32γ was not mandatory, but it increased the protective and inflammatory effects of BCG-induced training., Conclusions: BCG's ability to train innate immune cells, providing protection against leishmaniasis, as well as the participation of IL-32γ in this process, pave the way for new treatment strategies for this neglected infectious disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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31. Paracoccidioidesbrasiliensis induces IL-32 and is controlled by IL-15/IL-32/vitamin D pathway in vitro.
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Guimarães de Matos G, Barroso de Figueiredo AM, Diniz Gonçalves PH, Luiz de Lima Silva L, Bastista AC, Borges CL, Maria de Almeida Soares C, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Humans, Interleukin-15, Interleukins, Leukocytes, Mononuclear, Vitamin D, Paracoccidioides, Paracoccidioidomycosis
- Abstract
Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by Paracoccidioides spp., whose clinical outcome depends on immune response. Interleukin 32 (IL-32) is a cytokine present in inflammatory and infectious diseases, including bacterial, virus and protozoan infections. Its role in fungal disease remains unclear. The axis IL-15, IL-32 and vitamin D leads to microbicidal capacity against intracellular pathogens. Thus, the aims of this study were to investigate the production of IL-32 during Paracoccidioides spp. infection and whether this cytokine and IL-15 can increase P. brasiliensis control in a vitamin D dependent manner. IL-32 was highly detected in oral lesions from patients with PCM. In addition, high production of this cytokine was intracellularly detected in peripheral blood mononuclear cells (PBMCs) from healthy donors after exposure to particulated P. brasiliensis antigens (PbAg). The IL-32γ isoform was predominantly expressed, but there was mRNA alternative splicing for IL-32α isoform. The induction of IL-32 was dependent on Dectin-1 receptor. Infection of PBMCs with P. brasiliensis yeasts did not significantly induce IL-32 production even after activation with exogenous IFN-γ or IL-15 treatments. Although IL-15 was a potent inducer of IL-32 production, treatment with this cytokine did not increase the fungal control unless vitamin D was present in high levels. In this case, both IL-15 and IL-32 increased fungicidal activity of PBMCs. Together, data showed that IL-32 is present in lesions of PCM, PbAg induces IL-32, and the axis of IL-15/IL-32/vitamin D can contribute to control fungal infection. The data suggest that exposure to molecules from P. brasiliensis, as β-glucans, is needed to induce IL-32 production since only heat-killed and sonicated P. brasiliensis yeasts were able to increase IL-32, which was blocked by anti-Dectin-1 antibodies. This is the first description about IL-15/IL-32/vitamin D pathway role in P. brasiliensis infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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32. IL-15 enhances the capacity of primary human macrophages to control Leishmania braziliensis infection by IL-32/vitamin D dependent and independent pathways.
- Author
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Silva LLL, Gomes RS, Silva MVT, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Antiparasitic Agents pharmacology, Interleukin-15 pharmacology, Interleukins pharmacology, Leishmania braziliensis physiology, Recombinant Proteins metabolism, Signal Transduction, Vitamin D pharmacology, Antiparasitic Agents metabolism, Interleukin-15 metabolism, Interleukins metabolism, Leishmania braziliensis drug effects, Leishmaniasis, Cutaneous drug therapy, Vitamin D metabolism
- Abstract
How human macrophages can control the intracellular infection with Leishmania is not completely understood. IL-15 and IL-32 are cytokines produced by monocytes/macrophages that can induce antimicrobial mechanisms. Here, we evaluated the effects of recombinant human IL-15 (rhIL-15) on primary human macrophage infection and response to L. braziliensis. Priming with rhIL-15 reduced the phagocytosis of L. braziliensis and increased the killing of the parasites in monocyte-derived macrophages from healthy donors. rhIL-15 induced TNFα and IL-32 in uninfected cells. After infection, the high levels of rhIL-15-induced TNFα and IL-32 were maintained. In addition, there was an increase of NO and an inhibition of the parasite-induced IL-10 production. Inhibition of NO reversed the leishmanicidal effects of rhIL-15. Although rhIL-15 did not increase L. braziliensis-induced reactive oxygen intermediates (ROS) production, inhibition of ROS reversed the control of infection induced by rhIL-15. Treatment of the cells with rhIL-32γ increased microbicidal capacity of macrophages in the presence of high levels of vitamin D (25D3), but not in low concentrations of this vitamin. rhIL-15 together with rhIL-32 lead to the highest control of the L. braziliensis infection in high concentrations of vitamin D. In this condition, NO and ROS mediated rhIL-32γ effects on microbicidal activity. The data showed that priming of human macrophages with rhIL-15 or rhIL-32γ results in the control of L. braziliensis infection through induction of NO and ROS. In addition, rhIL-32γ appears to synergize with rhIL-15 for the control of L. braziliensis infection in a vitamin D-dependent manner., Competing Interests: Declaration of Competing Interest We declare that we do not have any potential sources of conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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33. Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.
- Author
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Dos Santos JC, Leite Quixabeira VB, Teodoro Silva MV, Damen MSMA, Schraa K, Jaeger M, Oosting M, Keating ST, Dorta ML, Alves Pinto S, Bugalho Duarte F, de Araújo Pereira LI, Netea MG, Ribeiro-Dias F, and Joosten LAB
- Subjects
- Adult, Aged, Brazil epidemiology, Cytokines genetics, Cytokines metabolism, Female, Gene Expression Regulation immunology, Humans, Lectins, C-Type genetics, Lectins, C-Type metabolism, Leishmaniasis, Cutaneous epidemiology, Leishmaniasis, Cutaneous immunology, Leishmaniasis, Cutaneous metabolism, Male, Middle Aged, Nod2 Signaling Adaptor Protein genetics, Nod2 Signaling Adaptor Protein metabolism, Protein Isoforms, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Genetic Predisposition to Disease, Genetic Variation, Interleukins genetics, Leishmania classification, Leishmaniasis, Cutaneous genetics
- Abstract
Interleukin-32 is a novel inflammatory mediator that has been described to be important in the immunopathogenesis and control of infections caused by Leishmania parasites. By performing experiments with primary human cells in vitro, we demonstrate that the expression of IL-32 isoforms is dependent on the time exposed to L. amazonensis and L. braziliensis antigens. Moreover, for the first time we show the functional consequences of three different genetic variations in the IL32 (rs4786370, rs4349147, rs1555001) modulating IL-32γ expression, influencing innate and adaptive cytokine production after Leishmania exposure. Using a Brazilian cohort of 107 American Tegumentary Leishmaniasis patients and a control cohort of 245 healthy individuals, the IL32 rs4786370 genetic variant was associated with protection against ATL, whereas the IL32 rs4349147 was associated with susceptibility to the development of localized cutaneous and mucosal leishmaniasis. These novel insights may help improve therapeutic strategies and lead to benefits for patients suffering from Leishmania infections., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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34. Identification and characterization of Paracoccidioides lutzii proteins interacting with macrophages.
- Author
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Tomazett MV, Baeza LC, Paccez JD, Parente-Rocha JA, Ribeiro-Dias F, and de Almeida Soares CM
- Subjects
- Animals, Cell Wall chemistry, Cell Wall metabolism, Fructose-Bisphosphate Aldolase genetics, Fructose-Bisphosphate Aldolase metabolism, Fungal Proteins genetics, Immobilized Proteins metabolism, Macrophages microbiology, Mice, Paracoccidioides metabolism, Protein Binding, Proteomics, RAW 264.7 Cells, Serine Proteases genetics, Serine Proteases metabolism, Fungal Proteins metabolism, Host-Pathogen Interactions, Macrophages metabolism, Membrane Proteins metabolism, Paracoccidioides physiology
- Abstract
Paracoccidioidomycosis (PCM), caused by thermodimorphic fungi of the Paracoccidioides genus, is a systemic disorder that involves the lungs and other organs. The adherence of pathogenic microorganisms to host tissues is an essential event in the onset of colonization and spread. The host-pathogen interaction is a complex interplay between the defense mechanisms of the host and the efforts of pathogenic microorganisms to colonize it. Therefore, the identification of fungi proteins interacting with host proteins is an important step understanding the survival strategies of the fungus within the host. In this paper, we used affinity chromatography based on surface proteomics (ACSP) to investigate the interactions of pathogen proteins with host surface molecules. Paracoccidioides lutzii extracts enriched of surface proteins were captured by chromatographic resin, which was immobilized with macrophage cell surface proteins, and identified by mass spectrometry. A total of 215 proteins of P. lutzii were identified interacting with macrophage proteins. In silico analysis classified those proteins according to the presence of sites for N- and O-glycosylation and secretion by classical and non-classical pathways. Serine proteinase (SP) and fructose-1,6-bisphosphate aldolase (FBA) were identified in our proteomics analysis. Immunolocalization assay and flow cytometry both showed an increase in the expression of these two proteins during host-pathogen interaction., (Copyright © 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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35. β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.
- Author
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Dos Santos JC, Barroso de Figueiredo AM, Teodoro Silva MV, Cirovic B, de Bree LCJ, Damen MSMA, Moorlag SJCFM, Gomes RS, Helsen MM, Oosting M, Keating ST, Schlitzer A, Netea MG, Ribeiro-Dias F, and Joosten LAB
- Subjects
- Adult, Aged, Animals, BCG Vaccine immunology, Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, Female, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells metabolism, Humans, Interleukin-1 metabolism, Leishmania braziliensis drug effects, Macrophages drug effects, Macrophages parasitology, Male, Mice, Transgenic, Middle Aged, Monocytes drug effects, Monocytes metabolism, Signal Transduction drug effects, Transcription, Genetic drug effects, Up-Regulation drug effects, Vaccination, Young Adult, Immunity drug effects, Interleukins metabolism, Leishmania braziliensis physiology, Leishmaniasis, Cutaneous prevention & control, beta-Glucans pharmacology
- Abstract
American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component β-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in vivo. This study represents a definitive characterization of the role of IL-32γ in the trained phenotype induced by β-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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36. Alterations in monocyte subsets and cytokine production after TLR activation in American Cutaneous Leishmaniasis.
- Author
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Quixabeira VBL, Pereira LIA, Veras PRV, da Costa ACV, Fonseca LG, Galdino H Jr, da Silva IA Jr, Morato CI, Pinto SA, Pereira AJCS, Dorta ML, Oliveira MAP, Gomes RS, and Ribeiro-Dias F
- Subjects
- Adult, Aged, Cytokines immunology, Female, Humans, Interleukin-10 immunology, Leishmaniasis, Cutaneous parasitology, Male, Middle Aged, Monocytes immunology, Young Adult, Leishmaniasis, Cutaneous immunology
- Abstract
Phenotypic and functional aspects of monocytes from Localized Cutaneous Leishmaniasis (LCL) patients were evaluated. The frequencies of monocyte subsets and TLR2/TLR4 expression were evaluated in fresh peripheral blood whereas cytokine production was evaluated in whole blood cell cultures stimulated with TLR agonists or Leishmania braziliensis antigen (Ag). CD16
+ monocytes frequency was increased in patients compared with controls. A TLR4 agonist (LPS) induced expression of TNF and IL-10 in monocyte subsets of patients and controls. The CD14+ CD16+ monocytes expressed higher levels of these cytokines than CD14+ CD16- cells. The levels of secreted TNF were higher in whole blood cell cultures from patients than controls after LPS/TLR4 or Ag stimulation. Whereas in controls there was a positive correlation between TNF and IL-10 levels, this was not observed in stimulated cell cultures from patients. The high levels of LPS-induced TNF were associated with the number of lesions and the percentages of CD14hi CD16+ monocytes. The levels of TLR2-induced TNF were also associated with number of lesions. All monocyte subsets from patients expressed higher levels of TLR2 and TLR4 than controls. Data suggest that systemically activated monocytes contribute for an imbalance in pro- and anti-inflammatory cytokine production during LCL, participating in the immunopathogenesis of the disease., (© 2019 John Wiley & Sons Ltd.)- Published
- 2019
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37. Metacyclogenesis of Leishmania (Viannia) guyanensis : a comprehensive study of the main transformation features in axenic culture and purification of metacyclic promastigotes by negative selection with Bauhinia purpurea lectin.
- Author
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Mendes BP, da Silva IA, DaMata JP, Castro-Gomes T, Vieira LQ, Ribeiro-Dias F, and Horta MF
- Abstract
Leishmania (Viannia) guyanensis is one species that causes cutaneous leishmaniasis in the New World. The incidence of infections with this parasite is probably underestimated and few studies exist on this species, despite its epidemiological importance. In particular, there are no studies concerning L. guyanensis metacyclogenesis and no technique for obtaining metacyclic promastigotes for this species is presently available. Here, we have studied L. guyanensis metacyclogenesis in axenic culture, describing the main changes that occur during this process, namely, in morphology and size, sensitivity to complement-mediated lysis, surface carbohydrates and infectivity to macrophages. We have shown that metacyclogenesis in L. guyanensis promastigotes is basically complete on the 4th day of culture, as determined by decreased body size, increased flagellum length, resistance to complement-mediated lysis and infectivity. We have also found that only a fraction of the parasites is agglutinated by Bauhinia purpurea lectin. The non-agglutinated parasites, which also peaked on the 4th day of culture, had all morphological traits typical of the metacyclic stage. This is the first report describing metacyclogenesis in L. guyanensis axenic promastigotes and a simple and efficient method for the purification of metacyclic forms. Furthermore, a model of human macrophage infection with L. guyanensis was established.
- Published
- 2019
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38. Dendritic cell line AP284 supports Th17 amplification.
- Author
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de Oliveira PG, Gomes CM, Ávila LR, Ribeiro-Dias F, Leenen PJM, and de Oliveira MAP
- Subjects
- Animals, Cell Differentiation, Cell Line metabolism, Cells, Cultured, Dendritic Cells metabolism, Interleukin-12 metabolism, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Th1 Cells immunology, Th17 Cells immunology, Toll-Like Receptor 7 metabolism, Toll-Like Receptors metabolism, Cell Culture Techniques methods, Dendritic Cells immunology, Th17 Cells metabolism
- Abstract
Dendritic cells (DC) have the unique ability to capture microorganisms and activate naive T lymphocytes. Obtaining DC derived from progenitors demands high cost and prolonged cultivation. Different immortalized DC has been isolated but most of them have immature phenotype and depending on growing factors or other stimuli to be used. In this study we characterized the cell line AP284 as a DC. AP284 cells express high levels of CD11b, MHC class II, 33D1 and CD209b. They also express high amounts of CD80 costimulatory molecule and different toll like receptors (TLR). After stimuli with TLR agonist they produce surprising amount of IL-12p40 related to IL-23 formation but not IL-12p70. They are also able to produce IL-6 and favor amplification of a Th17 but not Th1 profile. This DC line may be useful for a better understanding of factors and cellular interactions responsible for the induction of IL-12p40, IL-23 and Th17 generation., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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39. Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients.
- Author
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Oliveira IBN, Gomes RS, Gomides LF, Dos Santos JC, Carneiro MAD, Ribeiro-Dias F, and Diniz DS
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- Adult, Cytokines biosynthesis, Cytokines drug effects, Female, Humans, Immunologic Factors therapeutic use, Male, Middle Aged, Multiple Sclerosis drug therapy, Toll-Like Receptor 2 immunology, Toll-Like Receptor 4 immunology, Interferon-beta therapeutic use, Interleukin-10 biosynthesis, Multiple Sclerosis immunology, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha drug effects
- Abstract
Objective: Multiple sclerosis (MS) is a multifactorial chronic disease that affects the central nervous system (CNS). Toll-like receptors (TLRs) play a central role in cytokine production after pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and contribute to CNS damage in MS patients. Here, we evaluated the effects of interferon (IFN)-β treatment in TLR2 and TLR4-dependent cytokine production and mRNA expression in whole-blood cell cultures from MS patients., Methods: We evaluated cytokine production by ELISA from whole-blood cell culture supernatants and mRNA expression by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs)., Results: In patients treated with IFN-β, tumor necrosis factor (TNF)-α production after exposure to TLR2 agonist (Pam3Cys) was lower than in healthy controls and untreated MS patients. However, IFN-β treatment had no significant effect on TNF-α production after TLR4 agonist (LPS) stimulation. On the other hand, interleukin (IL)-10 production was increased in TLR4- but not in TLR2-stimulated whole-blood cell culture from MS patients under IFN-β treatment when compared to the controls. No differences in TNF-α or IL-10 mRNA expression in PBMCs from healthy controls and untreated or treated MS patients were detected, although PBMCs from treated patients presented higher levels of IL-32γ mRNA than those from controls., Conclusions: Our data suggest that IFN-β treatment alters the TLR-dependent immune response of PBMCs from MS patients. This may contribute to the beneficial effects of IFN-β treatment., (© 2019 S. Karger AG, Basel.)
- Published
- 2019
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40. Promastigote parasites cultured from the lesions of patients with mucosal leishmaniasis are more resistant to oxidative stress than promastigotes from a cutaneous lesion.
- Author
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Ávila LR, Gomes CM, Oliveira PG, Gomes RS, Vinaud MC, Dorta ML, Uliana SRB, Ribeiro-Dias F, and Oliveira MAP
- Subjects
- Animals, Antioxidants chemistry, Antioxidants metabolism, Culture Media chemistry, Female, Host-Parasite Interactions, Humans, Immunity, Innate, Leishmania braziliensis growth & development, Leishmania braziliensis isolation & purification, Leishmania braziliensis metabolism, Leishmaniasis, Diffuse Cutaneous immunology, Leishmaniasis, Diffuse Cutaneous metabolism, Leishmaniasis, Diffuse Cutaneous parasitology, Leishmaniasis, Mucocutaneous immunology, Leishmaniasis, Mucocutaneous metabolism, Leishmaniasis, Mucocutaneous parasitology, Life Cycle Stages physiology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide metabolism, Nitric Oxide Donors pharmacology, Nitroprusside pharmacology, Protozoan Proteins genetics, Protozoan Proteins metabolism, Antiprotozoal Agents pharmacology, Hydrogen Peroxide pharmacology, Leishmania braziliensis drug effects, Life Cycle Stages drug effects, Nitric Oxide pharmacology
- Abstract
Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species (ROS). The aim of this study was to evaluate the ability of parasites obtained from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and amastigotes from LCL or ML isolates produced similar amounts of NO in culture. Promastigotes from ML isolates were more resistant to NO and H
2 O2 than LCL parasites in a stationary phase, whereas amastigotes from LCL isolates were more resistant to NO. In addition, in the stationary phase, promastigote isolates from patients with ML expressed more thiol-specific antioxidant protein (TSA) than LCL isolates. Therefore it is suggested that infective promastigotes from ML isolates are more resistant to microbicidal mechanisms in the initial phase of infection. Subsequently, amastigotes lose this resistance. This behavior of ML parasites can decrease the number of parasites capable of stimulating the host immune response shortly after the infection establishment., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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41. Case Report: Atypical Cutaneous Leishmaniasis in a Patient with Mixed Leishmania guyanensis and Leishmania amazonensis Infection.
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Gosch CS, Resende BS, Amorim CB, Marques CP, Pereira LIA, Pinto SA, Uliana SRB, Coelho AC, Ribeiro-Dias F, and Dorta ML
- Subjects
- Aged, Amphotericin B therapeutic use, Antiprotozoal Agents therapeutic use, Brazil, DNA, Protozoan genetics, Fluorescent Antibody Technique, Indirect, Humans, Leishmania guyanensis isolation & purification, Leishmania mexicana isolation & purification, Leishmaniasis, Cutaneous drug therapy, Leishmaniasis, Cutaneous parasitology, Male, Molecular Typing, Rural Population, Skin parasitology, Skin pathology, Coinfection diagnosis, Coinfection parasitology, Leishmania guyanensis genetics, Leishmania mexicana genetics, Leishmaniasis, Cutaneous diagnosis
- Abstract
The disseminated form of leishmaniasis is a serious and rare disease, being diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main characteristic is the appearance of multiple pleomorphic lesions on the cutaneous surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and histopathological and immunological findings presented a mixed pattern that hindered diagnosis and therapeutic management. Molecular typing revealed a mixed infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis . Molecular identification of the agents responsible for ACL is important for adequate therapeutic planning, minimizing the possibility of sequellae that impact the quality of life of the patient.
- Published
- 2018
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42. Interleukin-32: An endogenous danger signal or master regulator of intracellular pathogen infections-Focus on leishmaniases.
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Dos Santos JC, Damen MSMA, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Animals, Cytokines immunology, Cytokines metabolism, Host-Parasite Interactions immunology, Humans, Inflammation Mediators metabolism, Interleukins metabolism, Intracellular Space parasitology, Leishmania physiology, Leishmaniasis metabolism, Leishmaniasis parasitology, Inflammation Mediators immunology, Interleukins immunology, Intracellular Space immunology, Leishmania immunology, Leishmaniasis immunology, Signal Transduction immunology
- Abstract
Interleukin 32 (IL-32) is an intracellular cytokine produced by immune and non immune cells after different stimuli. It contributes to inflammation and control of intracellular pathogens mainly by inducing proinflammatory cytokines and microbicidal molecules. Evidence is rising showing that IL-32 can be considered an endogenous danger signal after tissue injury, amplifying the inflammatory process and acquired immune responses. It seems to be a master regulator of intracellular infectious diseases. In this review, first the general properties of IL-32 are described followed by its role in the immunopathogenesis of inflammatory and infectious diseases. Roles of IL-32 in the control of infectious diseases caused by intracellular pathogens are reported, and later a focus on IL-32 in leishmaniases, diseases caused by an intracellular protozoan, is presented., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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43. Leishmania (Viannia) guyanensis in tegumentary leishmaniasis.
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Borges AF, Gomes RS, and Ribeiro-Dias F
- Subjects
- Animals, Disease Models, Animal, Humans, Immunity, Innate, Interleukin-17 biosynthesis, Interleukin-17 immunology, Leishmania guyanensis immunology, Leishmania guyanensis virology, Leishmaniasis, Cutaneous immunology, Leishmaniasis, Cutaneous parasitology, Leishmaniavirus physiology, Mice, Mucous Membrane immunology, Mucous Membrane parasitology, Nasopharynx immunology, Nasopharynx parasitology, Nasopharynx pathology, Severity of Illness Index, Host-Parasite Interactions immunology, Leishmania guyanensis pathogenicity, Leishmaniasis, Cutaneous pathology, Leishmaniavirus pathogenicity, Mucous Membrane pathology
- Abstract
Leishmania (Viannia) guyanensis is a causal agent of American tegumentary leishmaniasis (ATL). This protozoan has been poorly investigated; however, it can cause different clinical forms of ATL, ranging from a single cutaneous lesion to severe lesions that can lead to destruction of the nasopharyngeal mucosa. L. (V.) guyanensis and the disease caused by this species can present unique aspects revealing the need to better characterize this parasite species to improve our knowledge of the immunopathological mechanisms and treatment options for ATL. The mechanisms by which some patients develop a more severe form of ATL remain unclear. It is known that the host immune profile and parasite factors may influence the clinical manifestations of the disease. Besides intrinsic parasite factors, Leishmaniavirus RNA 1 (LRV1) infecting L. guyanensis can contribute to ATL immunopathogenesis. In this review, general aspects of L. guyanensis infection in humans and mouse models are presented.
- Published
- 2018
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44. Human Interleukin-32γ Plays a Protective Role in an Experimental Model of Visceral Leishmaniasis in Mice.
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Gomes RS, Silva MVT, Dos Santos JC, van Linge C, Reis JM, Teixeira MM, Pinto SA, Dorta ML, Bai X, Chan ED, Dinarello CA, Oliveira MAP, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Animals, Humans, Mice, Mice, Inbred BALB C, Mice, Transgenic, Models, Animal, Immunity, Innate immunology, Immunity, Innate physiology, Interleukins immunology, Interleukins physiology, Leishmania infantum immunology, Leishmaniasis, Visceral immunology, Protective Factors
- Abstract
Visceral leishmaniasis (VL) is a chronic parasitic disease caused by Leishmania infantum in the Americas. During VL, several proinflammatory cytokines are produced in spleen, liver, and bone marrow. However, the role of interleukin-32 (IL-32) has not been explored in this disease. IL-32 can induce production of proinflammatory cytokines in innate immune cells and polarize the adaptive immune response. Herein, we discovered that L. infantum antigens induced expression of mRNA mainly for the IL-32γ isoform but also induced low levels of the IL-32β transcript in human peripheral blood mononuclear cells. Furthermore, infection of human IL-32γ transgenic mice (IL-32γTg mice) with L. infantum promastigote forms increased IL-32γ expression in the spleen and liver. Interestingly, IL-32γTg mice harbored less parasitism in the spleen and liver than wild-type (WT) mice. In addition, IL-32γTg mice showed increased granuloma formation in the liver compared to WT mice. The protection against VL was associated with increased production of nitric oxide (NO), interferon gamma (IFN-γ), IL-17A, and tumor necrosis factor alpha by splenic cells restimulated ex vivo with L. infantum antigens. In parallel, there was an increase in the number of Th1 and Th17 T cells in the spleens of IL-32γTg mice infected with L. infantum IL-32γ induction of IFN-γ and IL-17A expression was found to be essential for NO production by splenic cells of infected animals. These data indicate that IL-32γ potentiates the Th1/Th17 immune response during experimental VL, thus contributing to the control of L. infantum infection., (Copyright © 2018 American Society for Microbiology.)
- Published
- 2018
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45. Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex.
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Herkert PF, Dos Santos JC, Hagen F, Ribeiro-Dias F, Queiroz-Telles F, Netea MG, Meis JF, and Joosten LAB
- Subjects
- Cell Proliferation, Humans, Inflammation Mediators metabolism, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear microbiology, Macrophages immunology, Macrophages metabolism, Macrophages microbiology, Models, Biological, Reactive Oxygen Species metabolism, Cryptococcosis metabolism, Cryptococcosis microbiology, Cryptococcus gattii physiology, Cytokines metabolism
- Abstract
Cryptococcal species vary in capsule and cell size, thermotolerance, geographic distribution, and affected populations. Cryptococcus gattii sensu stricto and C. deuterogattii affect mainly immunocompetent hosts; however, C. bacillisporus , C. decagattii , and C. tetragattii cause infections mainly in immunocompromised hosts. This study aimed to compare the capacities of different species of the C. gattii species complex to induce cytokines and antimicrobial molecules in human peripheral blood mononuclear cells (PBMCs). Cryptococcus bacillisporus and C. deuterogattii induced the lowest levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 among the five species of the C. gattii complex. Cryptococcus deuterogattii induced higher levels of IL-22 than those induced by C. tetragattii and the environmental species C. flavescens In addition, C. bacillisporus and C. gattii sensu stricto proliferated inside human monocyte-derived macrophages after 24 h of infection. All Cryptococcus species were able to generate reactive oxygen species (ROS) in human PBMCs, with C. bacillisporus and C. deuterogattii being more efficient than the other species. In conclusion, C. bacillisporus and C. deuterogattii induce lower levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and higher ROS levels than those induced by the other species. Species of the Cryptococcus gattii complex have different abilities to induce cytokine and ROS production by human PBMCs., (Copyright © 2018 American Society for Microbiology.)
- Published
- 2018
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46. Performance of two immunochromatographic tests for diagnosis of visceral leishmaniasis in patients coinfected with HIV.
- Author
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da Silva MRB, Brandão NAA, Colovati M, de Sousa MMP, de Lima LC, Dorta ML, Ribeiro-Dias F, Costa DL, Costa CHN, and de Oliveira MAP
- Subjects
- Adult, Antigens, Protozoan immunology, Brazil, Coinfection, Female, Humans, Leishmaniasis, Visceral complications, Male, Protozoan Proteins immunology, Sensitivity and Specificity, Chromatography, Affinity methods, HIV Infections complications, Leishmaniasis, Visceral diagnosis
- Abstract
Because of visceral leishmaniasis (VL) urbanization and spreading of the human immunodeficiency virus (HIV) infection to rural areas, coinfection has become more common. Here, we compared the accuracy of Kalazar Detect® (KD), an rK39-based immunochromatographic (IC) test, and OrangeLife® (OL), an rK39 + rK28 IC test, for diagnosing VL in patients coinfected with HIV in an endemic area in Brazil. Seventy-six VL patients and 40 patients with other diseases, of which 31 and 21 patients, respectively, were infected with HIV, were examined. The sensitivity of OL and KD tests was 88.89 and 95.45%, respectively, in patients without HIV. The sensitivity dropped to 67.74 and 61.29%, respectively, in coinfected patients. The decrease in sensitivity was not related to a decrease in the production of Leishmania-specific IgG. Because of the low sensitivity of rk39 test in HIV-infected patients, we suggest that patients with negative rK39 results should undergo further investigation with additional serological tests that are not based only on the rK39 antigen and examination of bone marrow aspirates.
- Published
- 2018
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47. TLR4 and TLR2 activation is differentially associated with age during Parkinson's disease.
- Author
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Rocha Sobrinho HMD, Silva DJD, Gomides LF, Dorta ML, Oliveira MAP, and Ribeiro-Dias F
- Subjects
- Adult, Aged, Cells, Cultured, Humans, Interleukin-10 metabolism, Lipopolysaccharides immunology, Lipoproteins immunology, Middle Aged, Risk, Toll-Like Receptor 2 agonists, Toll-Like Receptor 4 agonists, Tumor Necrosis Factor-alpha metabolism, Age Factors, Aging immunology, Parkinson Disease immunology, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by loss of dopaminergic neurons associated with neuroinflammation. Toll-like receptors (TLRs) are expressed in peripheral blood leukocytes and also in neurons and glial cells mediating inflammation. This study aimed to investigate the peripheral blood leukocyte response to TLR2 and TLR4 agonists in young and elderly PD patients. Two groups of patients with PD were evaluated (≤ 55 years old and ≥ 65 years old), age-matched with healthy controls (n = 26). Severity of PD was evaluated by Unified Parkinson's Disease Rating Scale (UPDRS). Whole blood cultures were stimulated with lipopolysaccharide (LPS), a TLR4 agonist or Pam
3 Cys (Pam), a TLR2 agonist. Tumor necrosis factor alpha (TNFα) and interleukin 10 (IL-10) were measured by immunoenzimatic assay. 6 h-TNFα production was increased after TLR4 stimulation, mainly in young PD patients, whereas TLR2-induced TNFα and IL-10 levels were decreased in PD patients independent of age (p < 0.05). A reverse correlation between LPS-induced TNFα production and age was observed in PD patients and controls, but TNFα induced by TLR2 agonist was not associated with age of PD patients or controls. TNFα production induced by TLR4 but not by TLR2 was reversely associated with the age at PD onset and disease duration. No associations between UPDRS scores and cytokine levels were detected. In conclusion, TLR4 and TLR2 responses seem to be differentially affected during PD. Data suggest that TLR2 deficiency in periphery is independent of age of the patients, age at PD onset, or PD duration.- Published
- 2018
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48. The NOD2 receptor is crucial for immune responses towards New World Leishmania species.
- Author
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Dos Santos JC, Damen MSMA, Oosting M, de Jong DJ, Heinhuis B, Gomes RS, Araújo CS, Netea MG, Ribeiro-Dias F, and Joosten LAB
- Subjects
- Adult, Aged, Cell Survival, Cells, Cultured, Cytokines metabolism, Female, Humans, Leukocytes, Mononuclear immunology, Male, Middle Aged, Netherlands, Phagosomes metabolism, Young Adult, Leishmania immunology, Leishmaniasis, Cutaneous immunology, Nod2 Signaling Adaptor Protein genetics, Nod2 Signaling Adaptor Protein metabolism, Polymorphism, Genetic
- Abstract
American Tegumentary Leishmaniasis is a chronic infection caused by Leishmania protozoan. It is not known whether genetic variances in NOD-like receptor (NLR) family members influence the immune response towards Leishmania parasites and modulate intracellular killing. Using functional genomics, we investigated whether genetic variants in NOD1 or NOD2 influence the production of cytokines by human PBMCs exposed to Leishmania. In addition, we examined whether recognition of Leishmania by NOD2 contributes to intracellular killing. Polymorphisms in the NOD2 gene decreased monocyte- and lymphocyte-derived cytokine production after stimulation with L. amazonensis or L. braziliensis compared to individuals with a functional NOD2 receptor. The phagolysosome formation is important for Leishmania-induced cytokine production and upregulation of NOD2 mRNA expression. NOD2 is crucial to control intracellular infection caused by Leishmania spp. NOD2 receptor is important for Leishmania recognition, the control of intracellular killing, and the induction of innate and adaptive immune responses.
- Published
- 2017
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49. Platelet-activating factor increases reactive oxygen species-mediated microbicidal activity of human macrophages infected with Leishmania (Viannia) braziliensis.
- Author
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Borges AF, Morato CI, Gomes RS, Dorta ML, de Oliveira MAP, and Ribeiro-Dias F
- Subjects
- Acetophenones pharmacology, Dihydropyridines pharmacology, Enzyme Inhibitors pharmacology, Gene Expression, Humans, Leishmania braziliensis growth & development, Macrophages immunology, Macrophages parasitology, NADPH Oxidases antagonists & inhibitors, NADPH Oxidases genetics, NADPH Oxidases metabolism, Platelet Activating Factor antagonists & inhibitors, Primary Cell Culture, Reactive Oxygen Species metabolism, Respiratory Burst drug effects, Leishmania braziliensis drug effects, Macrophages drug effects, Phagocytosis drug effects, Platelet Activating Factor pharmacology, Reactive Oxygen Species agonists
- Abstract
Platelet-activating factor (PAF) is produced by macrophages during inflammation and infections. We evaluated whether PAF is able to modulate the infection of human macrophages by Leishmania braziliensis, the main Leishmania sp. in Brazil. Monocyte-derived macrophages were incubated with promastigote forms in absence or presence of exogenous PAF. We observed that the treatment of macrophages with low concentrations of PAF prior to infection increased the phagocytosis of L. braziliensis. More importantly, exogenous PAF reduced the parasitism when it was added before, during or after infection. In addition, treatment with a PAF antagonist (PCA 4248) resulted in a significant increase of macrophage infection in a concentration-dependent manner, suggesting that endogenous PAF is important to control L. braziliensis infection. Mechanistically, while exogenous PAF increased production of reactive oxygen species (ROS) treatment with PCA 4248 reduced oxidative burst during L. braziliensis infection. The microbicidal effects of exogenous PAF were abolished when macrophages were treated with apocynin, an NADPH oxidase inhibitor. The data show that PAF promotes the production of ROS induced by L. braziliensis, suggesting that this lipid mediator may be relevant to control L. braziliensis infection in human macrophages., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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50. IL-32γ promotes the healing of murine cutaneous lesions caused by Leishmania braziliensis infection in contrast to Leishmania amazonensis.
- Author
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Gomes RS, Silva MVT, Dos Santos JC, de Lima Silva LL, Batista AC, Machado JR, Teixeira MM, Dorta ML, de Oliveira MAP, Dinarello CA, Joosten LAB, and Ribeiro-Dias F
- Subjects
- Animals, Disease Models, Animal, Humans, Interleukins genetics, Mice, Inbred C57BL, Mice, Transgenic, Skin parasitology, Skin pathology, Interleukins metabolism, Leishmania braziliensis immunology, Leishmania mexicana immunology, Leishmaniasis, Cutaneous immunology, Wound Healing
- Abstract
Background: Interleukin 32 (IL-32) is a pro-inflammatory cytokine induced in patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. Here, we investigated whether IL-32 is also expressed in patient lesions caused by L. amazonensis. In addition, we evaluated experimental L. amazonensis and L. braziliensis infections in C57BL/6 transgenic mice for human IL-32γ (IL-32γTg) in comparison with wild-type (WT) mice that do not express the IL-32 gene., Results: Human cutaneous lesions caused by L. amazonensis express higher levels of IL-32 than healthy control skin. In mice, the presence of IL-32γ promoted the control of cutaneous lesions caused by L. braziliensis, but not lesions caused by L. amazonensis in an ear dermis infection model. In addition, IL-32γTg mice displayed less tissue parasitism and inflammation in IL-32γTg than WT mice during the healing phase of L. braziliensis infection. Production of antigen-specific pro-inflammatory cytokines was higher in IL-32γTg mice than in WT mice during L. braziliensis infection but not during L. amazonensis infection., Conclusions: Human cutaneous lesions caused by L. amazonensis express high levels of IL-32. In mice, the presence of IL-32γ contributes to the lesion healing caused by L. braziliensis but not by L. amazonensis. Data suggest that despite the ability for both species to induce IL-32 in humans, the connections between this cytokine and other immune players induced by related species of parasites can lead to distinct outcomes of the murine infections.
- Published
- 2017
- Full Text
- View/download PDF
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