| Author | ASSUNÇÃO, S. F. V. de | |
| Author | ROSA, M. H. | |
| Author | CARVALHO, L. M. | |
| Author | NASCIMENTO, D. C. B. | |
| Author | FUZO, C. | |
| Author | CARVALHO, L. | |
| Author | BENEVIDES, L. | |
| Author | PEREIRA, V. C. | |
| Author | PACHECO, R. | |
| Author | CARVALHO FILHO, E. M. de | |
| Author | ZAMBONI, D. S. | |
| Author | ALVES FILHO, J. C. F. | |
| Author | SILVA, J. S. | |
| Access date | 2024-06-21T13:46:47Z | |
| Available date | 2024-06-21T13:46:47Z | |
| Document date | 2023 | |
| Citation | ASSUNÇÃO, S. F. V. de et al. SUCNR1-mediated response in CD11c+ macrophages is essential for the statement of resistance to cutaneous leishmaniasis. In: CONGRESS OF THE BRAZILIAN SOCIETY OF IMMUNOLOGY, 46, 2023, Ouro Preto, MG. Anais eletrônicos [...] Ouro Preto, MG: SBI, 02 a 6 de outubro de 2023. p.1-33. | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/64601 | |
| Language | eng | en_US |
| Publisher | Sociedade Brasileira de Imunologia | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Leishmaniose cutânea | en_US |
| Subject in Portuguese | SUCNR1 | en_US |
| Subject in Portuguese | Macrófagos | en_US |
| Title | SUCNR1-mediated response in CD11c+ macrophages is essential for the statement of resistance to cutaneous leishmaniasis | en_US |
| Type | Papers presented at events | en_US |
| Abstract | Cutaneous leishmaniasis (CL) is a neglected infectious disease prevalent in Brazil, where it is mainly caused by L. braziliensis and L. amazonensis. The available treatments are chronic and can lead to resistance to the parasites, hence, we investigate the role of succinate receptor 1 (SUCNR1) during the development of CL. SUCNR1 has been described in dendritic cells (DCs) and in macrophages (MOs) promoting inflammation. Therefore, we set to investigate SUCNR1 possible role during the development of CL. Our hypothesis is that SUCNR1 expressed by MOs and/or DCs contributes to the protective immune response to CL. We characterized SUCNR1 expression in the skin lesion of patients infected with L. brasiliensis, it is upregulated in the lesion and its expression is correlated with myeloid cell gene markers. To evaluate Sucnr1 role during CL, we infected wild type (WT) and Sucnr1 total knockout (Sucnr1-/-) mice with L. amazonensis and we observed an increase in the ear thickness, lesion, edema and parasite burden in the absence of Sucnr1. The cytokine profile in the lesion shift in Sucnr1-/- mice with a decrease in TNF, IL-12p70 and IFN-g but an increase in IL-4. Amongst the myeloid cells, we observed an increase in the infected CD11c+ MOs, they also presented a decreased intensity of iNOS. To confirm this finding, we differentiated BMDM from WT and Sucnr1-/- mice, and we performed a killing assay. We observed that Sucnr1-/- BMDM did not responded to IFN-g stimulus being unable to kill the parasites. We then constructed a conditional knockout mouse to Sucnr1 in CD11c+ cells (CD11ccreSucnr1f/f) and we infected them with L. amazonensis. The CD11ccreSucnr1f/f mice showed an increase in the ear thickness, lesion size, edema and parasite burden. Our data suggest that Sucnr1 expressed by CD11c+ macrophages are more responsive to IFN-g signalling which increases their ability of killing the parasite, thereby controlling the infection and the lesion progression during CL. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Plataforma Bi-Institucional de Pesquisa em Medicina Translacional. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade Federal da Sergipe. Aracaju, SE, Brasil. | en_US |
| Affilliation | Universidade Federal da Bahia. Salvador, BA, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Ribeirão Preto, SP, Brasil. | en_US |
| Subject | Cutaneous leishmaniasis | en_US |
| Subject | SUCNR1 | en_US |
| Subject | Macrophages | en_US |
| DeCS | Leishmaniose cutânea | en_US |
| DeCS | Macrófagos | en_US |
