Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Front Pediatr ; 7: 391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612120

RESUMO

Chronic granulomatous disease (CGD) is an inherited, genetically heterogeneous disease characterized by defective phagocytic cell microbicidal function, leading to increased susceptibility to bacterial and fungal infections. CGD is caused by mutations in components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, which is responsible for reactive oxygen species production during phagocytosis. Mutations in the neutrophil cytosolic factor 2 (NCF2) gene account for <5% of all cases. Here, we report a case of a 2-year-old female with persistent recurrent pneumopathy, even under trimethoprim-sulfamethoxazole (TMP-SMX) and itraconazole prophylaxis combined with IFNγ treatment. Genetic analysis revealed a novel homozygous mutation in NCF2, sequence depletion in a splicing region (c.256_257+2delAAGT NM_000433), leading to a K86Ifs*2 residue change in the p67-phox protein.

2.
Front Pediatr ; 6: 248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30255005

RESUMO

Chronic granulomatous disease (CGD) is an innate immune deficiency of phagocytic cells caused by mutations that affect components of the NADPH oxidase system, with resulting impairment in reactive oxygen species production. Patients with CGD are susceptible to recurrent infections and hyperinflammatory responses. Mutations in CYBB lead to the X-linked form of CGD and are responsible for ~ 70% of cases. In this study, we report the case of a 2.5-year-old male patient with recurrent pneumonia and Bacillus Calmette-Guérin infection (BCGitis). As his first clinical manifestation, he presented with bullous impetigo at 18 days of age, which was followed by recurrent pneumonia and regional BCGitis. Genetic analysis revealed a de novo mutation in exon 5 of the CYBB gene: a single-nucleotide substitution, c.376T > C, leading to a C126R change.

3.
Front Immunol ; 9: 567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666621

RESUMO

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a primary immunodeficiency caused by mutations in the autoimmune regulator gene (AIRE). Patients with AIRE mutations are susceptible to Candida albicans infection and present with autoimmune disorders. We previously demonstrated that cytoplasmic AIRE regulates the Syk-dependent Dectin-1 pathway. In this study, we further evaluated direct contact with fungal elements, synapse formation, and the response of macrophage-like THP-1 cells to C. albicans hyphae to determine the role of AIRE upon Dectin receptors function and signaling. We examined the fungal synapse (FS) formation in wild-type and AIRE-knockdown THP-1 cells differentiated to macrophages, as well as monocyte-derived macrophages from APECED patients. We evaluated Dectin-2 receptor signaling, phagocytosis, and cytokine secretion upon hyphal stimulation. AIRE co-localized with Dectin-2 and Syk at the FS upon hyphal stimulation of macrophage-like THP-1 cells. AIRE-knockdown macrophage-like THP-1 cells exhibited less Dectin-1 and Dectin-2 receptors accumulation, decreased signaling pathway activity at the FS, lower C. albicans phagocytosis, and less lysosome formation. Furthermore, IL-1ß, IL-6, or TNF-α secretion by AIRE-knockdown macrophage-like THP-1 cells and AIRE-deficient patient macrophages was decreased compared to control cells. Our results suggest that AIRE modulates the FS formation and hyphal recognition and help to orchestrate an effective immune response against C. albicans.


Assuntos
Candida albicans/imunologia , Hifas/imunologia , Macrófagos/imunologia , Fatores de Transcrição/imunologia , Candida albicans/fisiologia , Candidíase/genética , Candidíase/imunologia , Candidíase/microbiologia , Citocinas/imunologia , Citocinas/metabolismo , Células HEK293 , Humanos , Hifas/fisiologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Macrófagos/microbiologia , Mutação , Fagocitose/genética , Fagocitose/imunologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Poliendocrinopatias Autoimunes/microbiologia , Interferência de RNA , Células THP-1 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína AIRE
4.
PLoS One ; 6(7): e22141, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21799778

RESUMO

The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma cruzi. These conditions resulted in the marked modification of the PerC myelo-monocytic compartment characterized by the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated PerC displayed reduced staining for ß-galactosidase, a biomarker for senescence. Further, the adherent cells showed increased nitric oxide (NO) and higher frequency of IL-12-producing cells in response to subsequent LPS and IFN-γ stimulation. Among myelo-monocytic cells, SPM rather than LPM or monocytes, appear to be the central effectors of the activated PerC; they display higher phagocytic activity and are the main source of IL-12. Thus, our data provide a first demonstration of the consequences of the dynamics between peritoneal MØ subpopulations by showing that substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves PerC effector activity.


Assuntos
Diferenciação Celular , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/microbiologia , Cavidade Peritoneal/citologia , Cavidade Peritoneal/microbiologia , Trypanosoma cruzi/fisiologia , Animais , Antígenos de Diferenciação/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Parede Celular/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Antígenos HLA-D/metabolismo , Interleucina-12/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/microbiologia , Óxido Nítrico/metabolismo , Solubilidade , Trypanosoma cruzi/citologia , Zimosan/química , Zimosan/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA