Related Experiment Video
Updated: Mar 24, 2026
Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
PKC-δ activation in neutrophils promotes fungal clearance
Xun Li1, Xavier Cullere2, Hiroshi Nishi2
1Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Laboratory Medicine, The First Affiliated Hospital, Medical College of Xiamen University, Xiamen, Fujian, China;
Abstract:
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.
Insights
Protein kinase Cδ activation is crucial for neutrophil-mediated fungal killing, independent of Card9. This pathway is essential for host defense against Candida albicans and Aspergillus fumigatus infections.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Dectin-1 and Mac-1 are key receptors in fungal infection control.
- Neutrophils and macrophages play critical roles in host defense against fungal pathogens.
- Card9 is an important adaptor protein in innate immune responses.
Purpose of the Study:
- To investigate the role of protein kinase Cδ (PKCδ) in neutrophil and macrophage responses to fungal pathogens.
- To determine the relationship between PKCδ, Dectin-1, Mac-1, and Card9 signaling pathways.
- To assess the in vivo significance of PKCδ in fungal infections.
Main Methods:
- Utilized genetic deficiency models (PKCδ-deficient mice).
- Investigated cellular responses including reactive oxygen species (ROS) production, cytokine generation, phagolysosomal maturation, autophagy, and intracellular killing.
- Employed fungal models such as Candida albicans and Aspergillus fumigatus.
- Performed adoptive transfer of wild-type neutrophils into deficient mice.
Main Results:
- PKCδ activation, downstream of Dectin-1 and Mac-1, is essential for ROS production and intracellular killing of Candida albicans by neutrophils, independent of Card9.
- PKCδ is also required for zymosan-induced cytokine generation in neutrophils.
- In macrophages, PKCδ deficiency impaired fungi-induced ROS generation but did not affect Card9-related pathways (TAK1, NF-κB), phagolysosomal maturation, autophagy, or fungal killing.
- PKCδ-deficient mice exhibited high susceptibility to C. albicans and A. fumigatus infections, partially rescued by wild-type neutrophil transfer.
Conclusions:
- PKCδ activation downstream of Dectin-1 and Mac-1 plays a critical role in neutrophil-mediated host defense against fungal pathogens.
- Neutrophil PKCδ is essential for effective fungal clearance, while its role in macrophage antifungal activity is limited.
- Targeting PKCδ in neutrophils may represent a therapeutic strategy for fungal infections.
More Related Videos
Related Concept Videos
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions