RESUMO
Activation of mucosal-associated invariant T cells (MAIT cells) by certain bacteria, viruses, and yeast is well studied, but the activation potential of filamentous moulds from the order Mucorales is not known. Here, we show a rapid response of human MAIT cells against the Mucorales species Mucor circinelloides, Rhizopus arrhizus, and Rhizopus microsporus. This activation included upregulation of CD69 and degranulation marked by increased CD107a expression, while intracellular perforin and granzyme A expression were reduced. Furthermore, blocking of the antigen-presenting molecule major histocompatibility complex class I-related abrogated MAIT cell activation demonstrating a T cell receptor-dependent stimulation by Mucorales.
Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Mucorales/imunologia , Mucormicose/imunologia , Mucormicose/metabolismo , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Riboflavina/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Granzimas/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Mucor/imunologia , Mucormicose/microbiologia , Perforina/metabolismo , Rhizopus/imunologia , Rhizopus oryzae/imunologia , Regulação para CimaRESUMO
Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Neoplasias Hematológicas/complicações , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Mucor/efeitos dos fármacos , Mucor/imunologia , Mucor/isolamento & purificação , Mucorales/efeitos dos fármacos , Mucorales/imunologia , Mucorales/isolamento & purificação , Mucormicose/imunologia , Rhizopus oryzae/efeitos dos fármacos , Rhizopus oryzae/imunologia , Rhizopus oryzae/isolamento & purificaçãoRESUMO
Aim: To investigate the immune response of disseminated Ryzopus oryzae infection in immunocompetent mice. Methods: C57Bl/6, BALB/c and Swiss wild-type mice were intravenously infected with R. oryzae; the parameters of infection and immune response were determined. Transcriptional signature of Th17 immune response and infection in Il17ra-/- mice were also evaluated. Results: All mouse strains showed an initial spread of R. oryzae in the target tissues; however, after 30 days, C57Bl/6 and BALB/c mice showed an effective fungal clearance associated with specific production of IL-17 and IL-2. We also observed that 60% of Il17ra-/- mice succumbed to infection within 16 days. Conclusion: This study has established an immunocompetent model for disseminated mucormycosis and highlighted the role of IL-17 signaling in immunity against R. oryzae.
