The β-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance

Cell Host Microbe. 2011 Dec 15;10(6):603-15. doi: 10.1016/j.chom.2011.10.009.


Resistance to fungal infections is attributed to engagement of host pattern-recognition receptors, notably the β-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / immunology*
  • Candida albicans / physiology
  • Candidiasis / genetics
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Female
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Macrophage-1 Antigen / genetics
  • Macrophage-1 Antigen / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Phagocytosis
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / immunology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Signal Transduction


  • Lectins, C-Type
  • Macrophage-1 Antigen
  • Proto-Oncogene Proteins c-vav
  • Receptors, Immunologic
  • Vav1 protein, mouse
  • Vav3 protein, mouse
  • beta-glucan receptor
  • dectin 1