Enhanced Killing of Candida albicans by Human Macrophages Adherent to Type 1 Collagen Matrices via Induction of Phagolysosomal Fusion
AUTOR(ES)
Newman, Simon L.
FONTE
American Society for Microbiology
RESUMO
Candida albicans, a component of the normal flora of the alimentary tract and mucocutaneous membranes, is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients and of oropharyngeal disease in AIDS patients. As little is known about the regulation of monocyte/macrophage anti-Candida activity, we sought to determine if fungicidal activity might be regulated by extracellular matrix proteins to which monocytes/macrophages are adherent in vivo. Compared to monocyte/macrophages that adhered to plastic, human monocytes and monocyte-derived macrophages that adhered to type 1 collagen matrices, but not to fibronectin, vitronectin, or laminin, demonstrated a significant increase in candidacidal activity. The enhancement of monocyte fungicidal activity was maintained over a 4-h period, whereas macrophage fungicidal activity was maximum at 1 h. Although adherence of monocytes and macrophages to collagen matrices concomitantly enhanced the production of superoxide anion, only the fungicidal activity of collagen-adherent monocytes was partially blocked by superoxide dismutase and catalase. Remarkably, we found that only 10% of the phagosomes in C. albicans-infected macrophages that adhered to plastic fused with lysosomes. In contrast, 80% of yeast-containing phagosomes of collagen-adherent macrophages fused with lysosomes. These data suggest that nonoxidative mechanisms are critical for human macrophage anti-Candida activity and that C. albicans pathogenicity is mediated, in part, by its ability to inhibit phagolysosomal fusion in macrophages.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547032Documentos Relacionados
- Deletion of the SSK1 Response Regulator Gene in Candida albicans Contributes to Enhanced Killing by Human Polymorphonuclear Neutrophils
- Deletion of the Two-Component Histidine Kinase Gene (CHK1) of Candida albicans Contributes to Enhanced Growth Inhibition and Killing by Human Neutrophils In Vitro
- Enhanced killing of Candida albicans by cultured peritoneal exudate cells treated with SM-1213, a synthetic immunomodulator.
- Kinetics of Phagocytosis and Intracellular Killing of Candida albicans by Human Granulocytes and Monocytes
- Killing of Candida albicans by Human Salivary Histatin 5 Is Modulated, but Not Determined, by the Potassium Channel TOK1