101 results on '"Ribeiro-Dias F"'
Search Results
2. Non-specific effects of BCG in protozoal infections: tegumentary leishmaniasis and malaria
- Author
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dos Santos, J.C., Vilela Teodoro Silva, M., Ribeiro-Dias, F., and Joosten, L.A.B.
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- 2019
- Full Text
- View/download PDF
3. Protective immune response mediated by neutrophils in experimental visceral leishmaniasis is enhanced by IL-32 gamma
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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
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- 2022
4. 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, 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
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- 2021
5. Paracoccidioides brasiliensis induces IL-32 and is controlled by IL-15/IL-32/ vitamin D pathway in vitro
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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
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- 2021
6. 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)
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- 2020
7. 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.
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Item does not contain fulltext
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- 2020
8. 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)
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- 2019
9. The role of interleukin-32 in infections caused by New World Leishmania species and identification of novel treatment strategies
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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)
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- 2019
10. 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)
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- 2018
11. 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.
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- 2018
12. 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.
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- 2017
13. 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
14. 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)
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- 2017
15. 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
16. 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.
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- 2016
17. Interleukin 32gamma (IL-32gamma) is highly expressed in cutaneous and mucosal lesions of American Tegumentary Leishmaniasis patients: association with tumor necrosis factor (TNF) and IL-10
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Galdino, H., Jr., Maldaner, A.E., Pessoni, L.L., Soriani, F.M., Pereira, L.I., Pinto, S.A., Duarte, F.B., Gomes, C.M., Fleuri, A.K., Dorta, M.L., Oliveira, M.A. de, Teixeira, M.M., Batista, A.C., Joosten, L.A., Vieira, L.Q., Ribeiro-Dias, F., Galdino, H., Jr., Maldaner, A.E., Pessoni, L.L., Soriani, F.M., Pereira, L.I., Pinto, S.A., Duarte, F.B., Gomes, C.M., Fleuri, A.K., Dorta, M.L., Oliveira, M.A. de, Teixeira, M.M., Batista, A.C., Joosten, L.A., Vieira, L.Q., and Ribeiro-Dias, F.
- Abstract
Contains fulltext : 138334.pdf (publisher's version ) (Open Access), BACKGROUND: The interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis. METHODS: IL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32alpha, beta, delta, gamma mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP. RESULTS: We showed that the mRNA expression of IL-32, in particular IL-32gamma was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32gamma mRNA expression in PBMC from healthy individuals. CONCLUSIONS: These data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.
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- 2014
18. Mycoplasma arginini enhances cytotoxicity of thioglycollate-elicited murine macrophages toward YAC-1 tumor cells through production of NO
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Ribeiro-Dias F, Russo M, Ja, Marzagão Barbuto, Fr, Fernandes Do Nascimento, Timenetsky J, and sonia jancar
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Cytotoxicity, Immunologic ,Male ,Mice ,Mice, Inbred BALB C ,Mycoplasma ,Tumor Necrosis Factor-alpha ,Macrophages ,Thioglycolates ,Animals ,Mycoplasma Infections ,Nitric Oxide ,Chromosomes, Artificial, Yeast - Abstract
Bacterial products stimulate macrophage tumoricidal activity through release of tumor necrosis factor (TNF) and nitric oxide (NO). We show here that thioglycollate-elicited macrophages acquire cytotoxic activity when cocultured with Mycoplasma arginini-infected YAC-1 tumor cells and release TNF and NO. Fixed mycoplasma-infected cells, supernatants from infected-cell cultures, or purified heat-killed mycoplasma obtained from cell-free cultures were all able to induce TNF and NO production. Thus, the mycoplasma per se and not a product of infected cells induce the release of these molecules. Addition of prostaglandin E2 (PGE2) to the cocultures, which reduced TNF release, or antibodies to TNF, did not affect macrophage cytotoxicity nor NO release. Inhibition of NO production by L-NAME or aminoguanidine reduced the cytotoxicity, and treatment with a NO donor was toxic to YAC-1 cells. These results indicate that M. arginini activates thioglycollate-elicited murine macrophages for NO and TNF release increasing their cytotoxic activity toward YAC-1 cells and that this activity is dependent on NO but not TNF release.
- Published
- 1999
19. The molecular signature of oxidative metabolism and the mode of macrophage activation determine the shift from acute to chronic disease in experimental arthritis: critical role of interleukin-12p40.
- Author
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Takahashi, N., Jager, V.C.L. de, Gluck, A., Letzkus, M., Hartmann, N., Staedtler, F., Ribeiro-Dias, F., Heuvelmans-Jacobs, M., Berg, W.B. van den, Joosten, L.A.B., Takahashi, N., Jager, V.C.L. de, Gluck, A., Letzkus, M., Hartmann, N., Staedtler, F., Ribeiro-Dias, F., Heuvelmans-Jacobs, M., Berg, W.B. van den, and Joosten, L.A.B.
- Abstract
Contains fulltext : 70716.pdf (publisher's version ) (Closed access), OBJECTIVE: Repeated injection of streptococcal cell wall (SCW) fragments results in chronic arthritis in mice. The objective of this study was to identify genes and pathways that determine disease progression based on gene expression profiling in this model. METHODS: Chronic arthritis was induced in mice by 4 injections of SCW fragments. RNA samples were isolated from synovial tissue obtained at various time points and were analyzed using mouse genome array and quantitative reverse transcription-polymerase chain reaction techniques. The functional role of potential key genes was evaluated in mice with specific gene deletions. RESULTS: Gene expression analyses revealed a shift in molecular signature. In contrast to an up-regulation of the inflammatory response pathway, the pathways involved in oxidative metabolism were significantly down-regulated during the chronic phase of arthritis. Since oxidative metabolism determines the mode of macrophage activation, we investigated phenotype switching in macrophages. Markers of alternatively activated macrophages, such as arginase 1, were at maximal levels during acute inflammation. In contrast, induction of markers of classically activated macrophages (M1), such as interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS), was relatively low during the acute phase of disease, but highly increased toward the chronic phase. M1 polarization during the chronic phase was accompanied by a Th1 signature, characterized by IL-12p40, IL-12p35, and interferon-gamma. However, the absence of IL-12p40, but not IL-12p35, significantly inhibited the chronic phase of arthritis and was marked by a reduction in IL-17 and iNOS levels, as well as restored expression of oxidative metabolism genes. CONCLUSION: M1 polarization accompanied by a decline in oxidative metabolism determine the chronic phase of arthritis. IL-12p40, most likely acting through the IL-23/IL-17 axis, plays a critical role in this process.
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- 2008
20. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis.
- Author
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Abdollahi-Roodsaz, S., Joosten, L.A.B., Koenders, M.I., Devesa, I., Roelofs, M.F., Radstake, T.R.D.J., Heuvelmans-Jacobs, M., Akira, S., Nicklin, M.J., Ribeiro-Dias, F., Berg, W.B. van den, Abdollahi-Roodsaz, S., Joosten, L.A.B., Koenders, M.I., Devesa, I., Roelofs, M.F., Radstake, T.R.D.J., Heuvelmans-Jacobs, M., Akira, S., Nicklin, M.J., Ribeiro-Dias, F., and Berg, W.B. van den
- Abstract
Contains fulltext : 70944.pdf (publisher's version ) (Open Access), TLRs may contribute to the progression of rheumatoid arthritis through recognition of microbial or host-derived ligands found in arthritic joints. Here, we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of autoimmune arthritis and play distinct roles in the regulation of T cells and cytokines. We investigated the involvement of TLR2, TLR4, and TLR9 in the progression of arthritis using IL-1 receptor antagonist-knockout (IL1rn-/-) mice, which spontaneously develop an autoimmune T cell-mediated arthritis. Spontaneous onset of arthritis was dependent on TLR activation by microbial flora, as germ-free mice did not develop arthritis. Clinical and histopathological evaluation of IL1rn-/-Tlr2-/- mice revealed more severe arthritis, characterized by reduced suppressive function of Tregs and substantially increased IFN-gamma production by T cells. IL1rn-/-Tlr4-/- mice were, in contrast, protected against severe arthritis and had markedly lower numbers of Th17 cells and a reduced capacity to produce IL-17. A lack of Tlr9 did not affect the progression of arthritis. While any therapeutic intervention targeting TLR2 still seems complicated, the strict position of TLR4 upstream of a number of pathogenic cytokines including IL-17 provides an interesting potential therapeutic target for rheumatoid arthritis.
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- 2008
21. Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells
- Author
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Ribeiro-Dias, F., primary, Russo, M., additional, Nascimento, F.R.F., additional, Barbuto, J.A.M., additional, Timenetsky, J., additional, and Jancar, S., additional
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- 1998
- Full Text
- View/download PDF
22. The molecular signature of oxidative metabolism and the mode of macrophage activation determine the shift from acute to chronic disease in experimental arthritis: Ccitical role of interleukin-12p40.
- Author
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Takahashi N, de Jager VCL, Glück A, Letzkus M, Hartmann N, Staedtler F, Ribeiro-Dias F, Heuvelmans-Jacobs M, van den Berg WB, and Joosten LAB
- Abstract
OBJECTIVE: Repeated injection of streptococcal cell wall (SCW) fragments results in chronic arthritis in mice. The objective of this study was to identify genes and pathways that determine disease progression based on gene expression profiling in this model. METHODS: Chronic arthritis was induced in mice by 4 injections of SCW fragments. RNA samples were isolated from synovial tissue obtained at various time points and were analyzed using mouse genome array and quantitative reverse transcription-polymerase chain reaction techniques. The functional role of potential key genes was evaluated in mice with specific gene deletions. RESULTS: Gene expression analyses revealed a shift in molecular signature. In contrast to an up-regulation of the inflammatory response pathway, the pathways involved in oxidative metabolism were significantly down-regulated during the chronic phase of arthritis. Since oxidative metabolism determines the mode of macrophage activation, we investigated phenotype switching in macrophages. Markers of alternatively activated macrophages, such as arginase 1, were at maximal levels during acute inflammation. In contrast, induction of markers of classically activated macrophages (M1), such as interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS), was relatively low during the acute phase of disease, but highly increased toward the chronic phase. M1 polarization during the chronic phase was accompanied by a Th1 signature, characterized by IL-12p40, IL-12p35, and interferon-gamma. However, the absence of IL-12p40, but not IL-12p35, significantly inhibited the chronic phase of arthritis and was marked by a reduction in IL-17 and iNOS levels, as well as restored expression of oxidative metabolism genes. CONCLUSION: M1 polarization accompanied by a decline in oxidative metabolism determine the chronic phase of arthritis. IL-12p40, most likely acting through the IL-23/IL-17 axis, plays a critical role in this process. [ABSTRACT FROM AUTHOR]
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- 2008
- Full Text
- View/download PDF
23. A dysflagellar mutant of Leishmania (Viannia) braziliensis isolated from a cutaneous leishmaniasis patient
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Zauli Rogéria C, Yokoyama-Yasunaka Jenicer KU, Miguel Danilo C, Moura Alexandre S, Pereira Ledice IA, da Silva Ildefonso A, Lemes Lucianna GN, Dorta Miriam L, de Oliveira Milton AP, Pitaluga André N, Ishikawa Edna AY, Rodrigues Juliany CF, Traub-Cseko Yara M, Bijovsky A, Ribeiro-Dias Fátima, and Uliana Silvia RB
- Subjects
flagellum ,mutant ,Leishmania ,electron microscopy. ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Parasites of the Leishmania genus alternate between the flagellated extracellular promastigote stage and intracellular amastigotes. Here we report the characterization of a Leishmania isolate, obtained from a cutaneous leishmaniasis patient, which presents peculiar morphological features. Methods The parasite was cultured in vitro and characterized morphologically using optical and electron microscopy. Identification was performed based on monoclonal antibodies and internal ribosomal spacer typing. In vitro macrophage cultures, murine experimental models and sand fly infections were used to evaluate infectivity in vitro and in vivo. Results The isolate was identified as Leishmania (Viannia) braziliensis. In the atypical promastigotes grown in culture, a short flagellum surrounded or interrupted by a protuberance of disorganized material was observed. A normal axoneme was present close to the basal body but without elongation much further outside the flagellar pocket. A disorganized swelling at the precocious end of the axoneme coincided with the lack of a paraflagellar rod structure. The isolate was able to infect macrophages in vitro, induce lesions in BALB/c mice and infect Lutzomyia longipalpis. Conclusions Notwithstanding the lack of an extracellular flagellum, this isolate infects macrophages in vitro and produces lesions when inoculated into mice. Moreover, it is able to colonize phlebotomine sand flies. Considering the importance attributed to the flagellum in the successful infection and survival of Leishmania in the insect midgut and in the invasion of macrophages, these findings may bring new light into the infectious mechanisms of L. (V.) braziliensis.
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- 2012
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24. The role of interleukin-32 in infections caused by New World Leishmania species and identification of novel treatment strategies
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Dos Santos, J.C., Joosten, L.A.B., Ribeiro Dias, F., and Radboud University Nijmegen
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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
25. Leishmania braziliensis enhances monocyte responses to promote anti-tumor activity.
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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
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- 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.)
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- 2024
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26. 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
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- 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.)
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- 2024
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27. Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis .
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de Figueiredo AMB, Moraes D, Bailão AM, Rocha OB, Silva LOS, Ribeiro-Dias F, and Soares CMA
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- 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.)
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- 2023
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28. 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.
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- 2023
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29. Genome-Wide Association Study Reveals CLEC7A and PROM1 as Potential Regulators of Paracoccidioides brasiliensis -Induction of Cytokine Production in Peripheral Blood Mononuclear Cells.
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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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30. Lipophosphoglycan From Dermotropic New World Leishmania Upregulates Interleukin-32 and Proinflammatory Cytokines Through TLR4 and NOD2 Receptors.
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Silveira MB, Gomes RS, Shio MT, Rugani JN, Paranaiba LF, Soares RP, and Ribeiro-Dias F
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- 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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31. A Critical Overview of Interleukin 32 in Leishmaniases.
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Ribeiro-Dias F and Oliveira IBN
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- 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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32. 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
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- 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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33. 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 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.
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Tomazett MV, Baeza LC, Paccez JD, Parente-Rocha JA, Ribeiro-Dias F, and de Almeida Soares CM
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- 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.
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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. 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.
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- 2018
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37. Leishmania (Viannia) guyanensis in tegumentary leishmaniasis.
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Borges AF, Gomes RS, and Ribeiro-Dias F
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- 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.
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- 2018
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38. 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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39. 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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40. 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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41. 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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- View/download PDF
42. 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
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43. Susceptibility to Miltefosine in Brazilian Clinical Isolates of Leishmania ( Viannia ) braziliensis .
- Author
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Espada CR, Ribeiro-Dias F, Dorta ML, Pereira LIA, Carvalho EM, Machado PR, Schriefer A, Yokoyama-Yasunaka JKU, Coelho AC, and Uliana SRB
- Subjects
- Adolescent, Adult, Aged, Brazil, Child, Preschool, Humans, Inhibitory Concentration 50, Middle Aged, Phosphorylcholine therapeutic use, Young Adult, Drug Resistance, Leishmania braziliensis drug effects, Leishmania braziliensis isolation & purification, Phosphorylcholine analogs & derivatives
- Abstract
Leishmania ( Viannia ) braziliensis is the main causative species of tegumentary leishmaniasis in Brazil. In this study, we evaluated the susceptibility of 16 clinical isolates of L. ( V. ) braziliensis from different regions of Brazil to miltefosine in vitro. Half-maximal inhibitory concentrations of miltefosine varied from 22.9 to 144.2 μM against promastigotes and from 0.3 to 4.2 μM against intracellular amastigotes. No significant differences were found between isolates of different geographical origins. A clear correlation between the EC
50 against promastigotes and amastigotes within each isolate was found. These findings contribute to the evaluation of miltefosine's potential and limitations for the treatment of tegumentary leishmaniasis in Brazil.- Published
- 2017
- Full Text
- View/download PDF
44. Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species.
- Author
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Dos Santos JC, Heinhuis B, Gomes RS, Damen MS, Real F, Mortara RA, Keating ST, Dinarello CA, Joosten LA, and Ribeiro-Dias F
- Subjects
- Antimicrobial Cationic Peptides metabolism, Cell Line, Gene Expression, Gene Knockdown Techniques, Humans, Nitric Oxide metabolism, beta-Defensins metabolism, Cathelicidins, Cytokines metabolism, Interleukins metabolism, Leishmania braziliensis immunology, Leishmania mexicana immunology, Macrophages immunology, Macrophages parasitology
- Abstract
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-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα 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 β-defensin 2 production regulated by IL-32., Conclusions: Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.
- Published
- 2017
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45. Interleukin 32: a novel player in the control of infectious diseases.
- Author
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Ribeiro-Dias F, Saar Gomes R, de Lima Silva LL, Dos Santos JC, and Joosten LA
- Subjects
- Animals, Bacterial Infections metabolism, Humans, Models, Biological, Signal Transduction, Virus Diseases metabolism, Communicable Diseases metabolism, Interleukins metabolism
- Abstract
Interleukin 32 (IL-32) is a proinflammatory cytokine, expressed as 9 distinct isoforms. The most active isoform is the predominantly intracellular-functioning IL-32γ. 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., (© Society for Leukocyte Biology.)
- Published
- 2017
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46. Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFα and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner.
- Author
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Galdino H Jr, Saar Gomes R, Dos Santos JC, Pessoni LL, Maldaner AE, Marques SM, Gomes CM, Dorta ML, de Oliveira MA, Joosten LA, and Ribeiro-Dias F
- Subjects
- Adolescent, Adult, Animals, Female, Humans, Male, Mice, Mice, Knockout, Middle Aged, Interleukin-10 immunology, Leishmania braziliensis immunology, Macrophages immunology, Monocytes immunology, Toll-Like Receptor 4 immunology, Tumor Necrosis Factor-alpha immunology
- Abstract
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 IFNγ, TLR4 neutralizing antibodies, natural antagonist of TLR4 (Bartonella LPS), TLR4 agonist (E. coli LPS), and amastigote forms. The concentrations of tumor necrosis factor (TNFα) and interleukin 10 (IL-10) were assayed by ELISA and TLR4 expression by flow cytometry. Amastigotes forms of L. braziliensis induced TNFα and IL-10 production only in IFNγ-primed PBMCs. The TNFα 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 TNFα 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 TNFα and IL-10 induced by L. braziliensis amastigotes and that the parasites decrease TLR4 expression on monocyte surface., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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- View/download PDF
47. Leishmania (Viannia) braziliensis amastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection.
- Author
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Gomes CM, Ávila LR, Santos JC, Oliveira PG, Tomé FD, Pereira LI, Dorta ML, Lino RS Jr, Ribeiro-Dias F, and Oliveira MA
- Subjects
- Animals, Disease Models, Animal, Female, Humans, Interferon-gamma deficiency, Leishmaniasis, Cutaneous genetics, Leishmaniasis, Cutaneous pathology, Macrophages immunology, Macrophages metabolism, Macrophages parasitology, Male, Mice, Mice, Knockout, Nitric Oxide Synthase Type II deficiency, Parasite Load, Phagocytosis, Leishmania braziliensis, Leishmaniasis, Cutaneous metabolism, Leishmaniasis, Cutaneous microbiology, Nitric Oxide metabolism
- Abstract
Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
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48. Identification and Biological Characterization of Leishmania (Viannia) guyanensis Isolated from a Patient with Tegumentary Leishmaniasis in Goiás, a Nonendemic Area for This Species in Brazil.
- Author
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Pires Ada S, Borges AF, Cappellazzo Coelho A, Dorta ML, Lino Junior Rde S, Pereira LI, Pinto SA, Pelli de Oliveira MA, de Matos GG, Abrahamsohn IA, Uliana SR, Lima GM, and Ribeiro-Dias F
- Subjects
- Animals, Brazil, Humans, Leishmania braziliensis isolation & purification, Leishmania guyanensis isolation & purification, Leishmaniasis, Cutaneous pathology, Mice, Leishmania braziliensis pathogenicity, Leishmania guyanensis pathogenicity, Leishmaniasis, Cutaneous parasitology
- Abstract
The aim of this study was to characterize clinical field isolates of Leishmania spp. obtained from patients with American Tegumentary Leishmaniasis (ATL) who live in Goiás state, Brazil. The presumed areas of infection were in Goiás, Tocantins, and Pará states. Three isolates of parasites were identified as L. (Viannia) braziliensis and one as L. (V.) guyanensis. The in vitro growth profiles were found to be similar for all parasites. Nevertheless, in C57BL/6 mice, L. (V.) guyanensis infection was better controlled than L. (V.) braziliensis. Yet in C57BL/6 mice deficient in interferon gamma, L. (V.) guyanensis lesions developed faster than those caused by L. (V.) braziliensis isolates. In BALB/c mice, the development of lesions was similar for isolates from both species; however, on the 11th week of infection, amastigotes could not be observed in macrophages from L. (V.) guyanensis-infected mice. Thus, L. (V.) guyanensis can be circulating in Goiás, a state where autochthonous cases of this species had not yet been reported. Considering the difficulties to differentiate L. (V.) guyanensis from L. (V.) braziliensis at the molecular, morphological, and clinical (human and murine models) levels, the presence of L. (V.) guyanensis infections is possibly underestimated in several regions of Brazil.
- Published
- 2015
- Full Text
- View/download PDF
49. In vitro metacyclogenesis of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis clinical field isolates, as evaluated by morphology, complement resistance, and infectivity to human macrophages.
- Author
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da Silva IA Jr, Morato CI, Quixabeira VB, Pereira LI, Dorta ML, de Oliveira MA, Horta MF, and Ribeiro-Dias F
- Subjects
- Antibodies, Monoclonal immunology, Cells, Cultured, Humans, In Vitro Techniques, Interferon-gamma immunology, Lectins immunology, Leishmania braziliensis isolation & purification, Leishmaniasis, Cutaneous immunology, Leishmaniasis, Cutaneous parasitology, Lipopolysaccharides immunology, Complement System Proteins immunology, Leishmania braziliensis cytology, Leishmania braziliensis immunology, Life Cycle Stages immunology, Macrophages immunology, Macrophages parasitology
- Abstract
This study was designed to assess in vitro metacyclogenesis of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis clinical field isolates obtained from patient lesions (L. braziliensis IMG3 and PPS6m; L. amazonensis MAB6). Metacyclogenesis was evaluated by different criteria, namely, promastigote size (morphometric analysis and flow cytometry), surface modifications (loss of lectin or monoclonal antibody (mAb) binding, complement resistance), and infectivity to human macrophages. Growth curves were similar for all parasites evaluated. The various features analyzed were expressed in a high percentage of promastigotes at 6th and 10th days of culture and a low percentage at the 2nd day. However, in most isolates, these features, considered as markers of metacyclogenesis, seemed to develop with different time courses, since the percentages of metacyclic forms detected with each technique were usually different. Parasites from 6th or 10th day and those negatively selected with lectin or mAb similarly infected human macrophages. From all isolates analyzed, L. amazonensis PH8 and MAB6 showed the highest and the lowest levels of susceptibility, respectively, to leishmanicidal activity of IFN-γ/LPS-activated macrophages. Our results showed that by using different techniques to evaluate different aspects of metacyclogenesis (morphological and biochemical modifications) different percentages of metacyclic promastigotes can be detected in each isolate culture.
- Published
- 2015
- Full Text
- View/download PDF
50. Essential role of leukotriene B4 on Leishmania (Viannia) braziliensis killing by human macrophages.
- Author
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Morato CI, da Silva IA Jr, Borges AF, Dorta ML, Oliveira MA, Jancar S, Serezani CH, and Ribeiro-Dias F
- Subjects
- Cell Survival, Cells, Cultured, Host-Pathogen Interactions, Humans, Macrophages parasitology, Reactive Oxygen Species metabolism, Leishmania braziliensis immunology, Leishmania braziliensis physiology, Leukotriene B4 metabolism, Macrophages drug effects, Macrophages immunology, Receptors, Leukotriene B4 metabolism
- Abstract
Although Leishmania (Viannia) braziliensis is the most prevalent species that cause American tegumentary leishmaniasis (ATL), the immune response against this parasite has been poorly investigated. Upon activation, macrophages produce a series of pro-inflammatory molecules, including the lipid mediator leukotriene B4 (LTB4). LTB4 has been shown to enhance several macrophage functions, but its role in human macrophages is less known. Here, we investigated the role of LTB4 on human monocyte-derived macrophages infected with human isolate of L. (V.) braziliensis (IMG3). It was found that human macrophages produce LTB4 upon infection with Leishmania, which by autocrine or paracrine activation of its high affinity receptor BLT1, potentiates macrophage leishmanicidal activity. This LTB4 effect is mediated by increased secretion of reactive oxygen species (ROS). Moreover, Leishmania infection decreased the expression of BLT1, leading to the speculation that this could represent a parasite escape mechanism to establish a chronic inflammatory infection. Therefore, our data suggest that LTB4 could be used in therapeutic strategies to control Leishmania infection., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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