The ß-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance.
Cell Host Microbe
; 10(6): 603-15, 2011 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-22177564
ABSTRACT
Resistance to fungal infections is attributed to engagement of host pattern-recognition receptors, notably the ß-glucan receptor Dectin-1 and the integrin Mac-1, which induce phagocytosis and antifungal immunity. However, the mechanisms by which these receptors coordinate fungal clearance are unknown. We show that upon ligand binding, Dectin-1 activates Mac-1 to also recognize fungal components, and this stepwise process is critical for neutrophil cytotoxic responses. Both Mac-1 activation and Dectin-1- and Mac-1-induced neutrophil effector functions require Vav1 and Vav3, exchange factors for RhoGTPases. Mac-1- or Vav1,3-deficient mice have increased susceptibility to systemic candidiasis that is not due to impaired neutrophil recruitment but defective intracellular killing of C. albicans yeast forms, and Mac-1 or Vav1,3 reconstitution in hematopoietic cells restores resistance. Our results demonstrate that antifungal immunity depends on Dectin-1-induced activation of Mac-1 functions that is coordinated by Vav proteins, a pathway that may localize cytotoxic responses of circulating neutrophils to infected tissues.
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Base de dados:
MEDLINE
Assunto principal:
Candida albicans
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Candidíase
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Receptores Imunológicos
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Antígeno de Macrófago 1
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Lectinas Tipo C
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Proteínas Proto-Oncogênicas c-vav
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Neutrófilos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article