Author | Carneiro, Pedro Paulo | |
Author | Dórea, Andreza Santos | |
Author | Oliveira, Walker | |
Author | Guimarães, Luiz Henrique | |
Author | Brodskyn, Cláudia Ida | |
Author | Carvalho, Edgar M. | |
Author | Bacellar, Olívia | |
Access date | 2024-01-17T14:06:10Z | |
Available date | 2024-01-17T14:06:10Z | |
Document date | 2022 | |
Citation | CARNEIRO, Pedro Paulo et al. Blockade of TLR2 and TLR4 attenuates inflammatory response and parasite load in cutaneous leishmaniasis. In: CONGRESSO WORLD LEISH7, 7, 2022., Colômbia. Anais eletrônicos [...] Colômbia: CIDEPRO, 23 agosto, 2022. p.1-16. | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/62220 | |
Sponsorship | The National Institutes Of Health. | en_US |
Language | eng | en_US |
Publisher | CIDEPRO | en_US |
Rights | open access | en_US |
Subject in Portuguese | Leishmaniose cutânea | en_US |
Subject in Portuguese | Leishmania braziliensis | en_US |
Subject in Portuguese | Receptores semelhantes a pedágio | en_US |
Subject in Portuguese | Imunidade inata | en_US |
Subject in Portuguese | Citocinas | en_US |
Title | Blockade of TLR2 and TLR4 attenuates inflammatory response and parasite load in cutaneous leishmaniasis | en_US |
Type | Papers presented at events | en_US |
Abstract | Human cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a strong inflammatory response that is associated with the ulcer development. Monocytes / macrophages are the main cells that harbor the parasite and are also responsible for parasites control. Toll-like receptors signaling pathway (TLR) is the first pathogen defense systems and leads to the transcription of inflammatory mediators such as the production of IL-1β and TNF during the innate immune response. We recently showed that in vitro infection with L. braziliensis caused CL monocytes to upregulate TLR2 and TLR4 expression, which was associated with TNF production. As TLR antagonist molecules have been used in the treatment of inflammatory diseases, our hypothesis is that the neutralization of these receptors may attenuate the strong inflammatory response observed in this disease. The aim of this study is to evaluate the role of TLR2 and TLR4 antagonists in the modulation of exaggerated inflammatory immune response observed in CL. Monocytes from CL patients and healthy subjects (HS) were treated with anti-TLR2 and anti-TLR4 and infected with L.braziliensis. The evaluation of infection and the parasite load was evaluated after cytospin preparations by optical microscopy. The expression of the oxidative burst, TNF, IL1β, IL-10, CXCL9 and CXCL10 were analyzed by flow cytometry. Cells from CL lesions were also treated with anti-TLR2 and anti-TLR4 and the evaluation of chemokine and cytokine production by these cells was performed by enzyme-linked assay (ELISA). We observed that after neutralization of these receptors, the number of infected cells and the number of internalized parasites decreased in monocytes from CL patients. TLR2 and TLR4 neutralization also decrease oxidative burst as well IL-1β, TNF and CXCL9 production by monocytes from CL patients. Also, TNF production by cells from CL lesions decreased after TLR2 and TLR4 neutralization. The attenuation of host inflammatory response after neutralizing these receptors suggests the potential of TLR antagonists as immunomodulators in association with antimonial therapy in human cutaneous leishmaniasis. | en_US |
Affilliation | Universidade Federal da Bahia. Hospital Universitário Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | en_US |
Affilliation | Universidade Federal da Bahia. Hospital Universitário Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | en_US |
Affilliation | Universidade Federal da Bahia. Hospital Universitário Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil. | en_US |
Affilliation | Universidade Federal do Sul da Bahia. Itabuna, BA, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, Bahia, Brasil. | en_US |
Affilliation | Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT). Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, Bahia, Brasil. | en_US |
Affilliation | Universidade Federal da Bahia. Hospital Universitário Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT). Salvador, BA, Brasil. | en_US |
Subject | Cutaneous leishmaniasis | en_US |
Subject | Leishmania braziliensis | en_US |
Subject | Toll-like receptors | en_US |
Subject | Innate immunity | en_US |
Subject | Cytokines | en_US |
DeCS | Leishmaniose cutânea | en_US |
DeCS | Leishmania braziliensis | en_US |
DeCS | Imunidade inata | en_US |
DeCS | Citocinas | en_US |