PKC-δ activation in neutrophils promotes fungal clearance

J Leukoc Biol. 2016 Sep;100(3):581-8. doi: 10.1189/jlb.4A0915-405R. Epub 2016 Mar 10.


The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- and Mac-1-induced activation of protein kinase Cδ in neutrophils, independent of the Card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon Candida albicans uptake. Protein kinase Cδ was also required for zymosan-induced cytokine generation in neutrophils. In macrophages, protein kinase Cδ deficiency prevented fungi-induced reactive oxygen species generation but had no effect on activation of TGF-β-activated kinase-1, an effector of Card9, or nuclear factor κB activation, nor did it affect phagolysosomal maturation, autophagy, or intracellular C. albicans killing. In vivo, protein kinase Cδ-deficient mice were highly susceptible to C. albicans and Aspergillus fumigatus infection, which was partially rescued with adoptively transferred wild-type neutrophils. Thus, protein kinase Cδ activation downstream of dectin-1 and Mac-1 has an important role in neutrophil, but not macrophage, functions required for host defense against fungal pathogens.

Keywords: C. albicans; Mac-1; dectin-1; host defense; reactive oxygen species; signaling.

MeSH terms

  • Animals
  • Aspergillosis / immunology*
  • Aspergillosis / metabolism
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / immunology
  • CARD Signaling Adaptor Proteins / physiology
  • Candida albicans / immunology
  • Candidiasis / immunology*
  • Candidiasis / metabolism
  • Candidiasis / microbiology
  • Cytokines / metabolism
  • Female
  • Lectins, C-Type / metabolism
  • Macrophage-1 Antigen / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Phagocytosis
  • Protein Kinase C-delta / physiology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta


  • CARD Signaling Adaptor Proteins
  • Card9 protein, mouse
  • Cytokines
  • Lectins, C-Type
  • Macrophage-1 Antigen
  • NF-kappa B
  • Reactive Oxygen Species
  • Transforming Growth Factor beta
  • dectin 1
  • Prkcd protein, mouse
  • Protein Kinase C-delta