Assuntos
Anticorpos Antifúngicos/sangue , Doença de Crohn/imunologia , Saccharomyces cerevisiae/imunologia , Ácido Úrico/sangue , Adulto , Anticorpos Antifúngicos/imunologia , Estudos de Coortes , Doença de Crohn/sangue , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Saccharomyces cerevisiae/patogenicidadeRESUMO
Mannose-binding lectin (MBL) is a soluble lectin of the innate immune system that is produced by the liver and secreted into the circulation where it activates the lectin complement pathway, enhances phagocytosis of microorganisms by leukocytes, and modulates inflammation. MBL can recognize patterns on the surface of different pathogens, including Candida albicans. Our aims were to investigate whether MBL is expressed in the gut epithelium and to examine its effect on the modulation of intestinal inflammation and C. albicans elimination. Using reverse transcriptase-PCR, MBL transcripts were highly expressed in different parts of the mouse gut. MBL expression was also detected by immunoblotting and immunolocalization in response to C. albicans colonization of the gut; the highest expression of MBL was detected in the stomach. Blocking MBL by administering mannans to mice increased C. albicans colonization. MBL-deficient mice had a higher level of colonization than wild-type mice. Dextran sodium sulfate-induced colitis promoted C. albicans dissemination to the kidneys and lungs of MBL-deficient mice. MBL-deficient mice exhibited elevated expression of interleukin (IL)-17, IL-23, dectin-1, and Toll-like receptor-4. This study shows that MBL expression is induced in the gut in response to C. albicans sensing and is required for intestinal homeostasis and host defense against C. albicans.
Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Colite/imunologia , Mucosa Intestinal/metabolismo , Lectina de Ligação a Manose/metabolismo , Animais , Células Cultivadas , Lectina de Ligação a Manose da Via do Complemento , Sulfato de Dextrana , Feminino , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Imunidade nas Mucosas , Interleucina-17/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Lectina de Ligação a Manose/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagocitose , Receptor 4 Toll-Like/metabolismoRESUMO
The diagnosis of systemic Candida infections is a recognized challenge. We developed a mass spectrometry strategy to detect signals from Candida molecules in patients' sera. Pre-analytical procedures were designed to extract oligosaccharides from serum. A peak m/z of at 365 was specifically revealed in sera from patients with candidaemia with regard to healthy controls. This biomarker was identified as a disaccharide, its presence did not correlate with mannanaemia or glucanaemia. Mouse models of Candida albicans colonization and infection showed that the signal was specifically associated with tissue invasion, suggesting that clinical evaluation of its usefulness in discriminating colonized and infected patients would be worthwhile.
