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Molari, Wilson Santos
;
Jmel, Mohamed Amine
;
Assis, Josiane Betim
;
Frazao-Silva, Alan
;
Bernardi, Julia Moura
;
Huamanrayme, Gretta
;
Medina, Jose Maria
;
Esteves, Eliane
;
Antao, Solange Cristina
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Costa, Gabriel Cerqueira Alves
;
Tanaka, Aparecida Sadae
;
Fogaca, Andrea Cristina
;
Franta, Zdenek
;
Tirloni, Lucas
;
Kotsyfakis, Michalis
;
Sa-Nunes, Anderson
Número total de Autores: 16
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| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN IMMUNOLOGY; v. 16, p. 16-pg., 2025-07-17. |
| Resumo | |
Introduction The Neotropical tick Amblyomma sculptum is the primary vector of Rickettsia rickettsii, the causative agent of Brazilian spotted fever, a disease associated with high fatality rates. Tick saliva, a complex mixture of bioactive molecules essential for successful blood feeding, facilitates pathogen transmission and modulates host immune responses. A comprehensive evaluation of the salivary gland transcriptome database reveals that protease inhibitors are abundantly expressed molecules in tick saliva during feeding. Thus, this study aims to describe and characterize the most expressed member of the cystatin family identified in Amblyomma sculptum salivary transcriptome, named Amblyostatin-1.Methods Bioinformatic tools were employed for in silico analysis of the Amblyostatin-1 sequence and structure. A recombinant version of Amblyostatin-1 was expressed in an Escherichia coli system, evaluated against a panel of cysteine proteases in biochemical assays, and used to generate antibodies in immunized mice. The biological activities of Amblyostatin-1 were assessed by its effects on dendritic cell maturation in vitro and in a carrageenan-induced inflammation model in vivo.Results Based on its sequence and predicted three-dimensional structure, Amblyostatin-1 is classified as an I25B cystatin, and its recombinant form selectively inhibits cathepsins L, C, and S at different rates, with a low nanomolar Ki value of 0.697 +/- 0.22 nM against cathepsin L. Regarding its biological activities, recombinant Amblyostatin-1 partially affects LPS-induced dendritic cell maturation by downmodulating the costimulatory molecules CD80 and CD86 at higher micromolar concentrations (3 mu M) while promoting IL-10 production at nanomolar concentrations (100 nM). The apparent lack of Amblyostatin-1-specific antibody responses in immunized mice suggests an impairment of antigen processing and presentation in vivo. Furthermore, in a carrageenan-induced inflammation model, Amblyostatin-1 decreased edema formation and neutrophil infiltration into the skin without affecting other myeloid cells.Discussion These findings establish Amblyostatin-1 as a novel salivary cystatin with immunomodulatory and anti-inflammatory properties, highlighting its potential as an immunobiological agent. (AU) | |
| Processo FAPESP: | 22/02742-3 - Caracterização molecular, bioquímica e imunológica de inibidores de proteases salivares de Amblyomma sculptum: do desenvolvimento de imunobiológicos a estratégias anti-carrapato |
| Beneficiário: | Anderson de Sá Nunes |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/07724-3 - Amblyostatina-1, primeira cistatina salivar de Amblyomma sculptum: alvos bioquímicos, atividade biológicas e potencial uso como vacina e imunobiológico. |
| Beneficiário: | Wilson Santos Molari |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 23/07831-7 - Amblyostatina-1, primeira cistatina salivar de Amblyomma sculptum: alvos bioquímicos, atividade biológicas e potencial uso como vacina e imunobiológico |
| Beneficiário: | Wilson Santos Molari |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Mestrado |
| Processo FAPESP: | 24/22525-2 - Identificação de antígenos intestinais de Rhipicephalus microplus através do uso de phage display |
| Beneficiário: | Gabriel Cerqueira Alves Costa |
| Modalidade de apoio: | Bolsas no Brasil - Programa Fixação de Jovens Doutores |
| Processo FAPESP: | 19/03779-5 - Uso de phage display como ferramenta no diagnóstico e controle de doenças transmitidas por vetores hematófagos |
| Beneficiário: | Aparecida Sadae Tanaka |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 20/16462-7 - Caracterização funcional de componentes do sistema imune, da saliva e da microbiota de carrapatos Amblyomma spp. no estabelecimento da infecção por Rickettsia rickettsii |
| Beneficiário: | Andréa Cristina Fogaça |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |