Related Experiment Video

Updated: Jan 23, 2026

Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
12:29

Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus

Published on: April 19, 2017

10.7K

Dok3-protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity

Jia Tong Loh1, Shengli Xu1,2, Jian Xin Huo1

  • 1Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore.

The Journal of Clinical Investigation
|June 11, 2019
PubMed

Insights

Downstream of kinase 3 (Dok3) adaptor suppresses antifungal immunity. Dok3 deficiency enhances neutrophil responses against Candida albicans, offering new therapeutic targets for invasive fungal infections.

Area of Science:

  • Immunology
  • Molecular Biology
  • Mycology

Background:

  • Invasive fungal infections pose significant health risks, with limited treatment options.
  • The precise mechanisms of host defense against fungal pathogens are not fully understood.

Purpose of the Study:

  • To investigate the role of the downstream of kinase 3 (Dok3) adaptor in regulating neutrophil-mediated antifungal immunity.
  • To identify potential therapeutic targets for combating invasive fungal infections like candidemia.

Main Methods:

  • Utilized a mouse model of systemic Candida albicans infection.
  • Assessed neutrophil functions including phagocytosis, cytokine production, and netosis.
  • Employed biochemical assays to elucidate the interaction between Dok3, protein phosphatase 1 (PP1), and Card9 signaling.

Main Results:

  • Dok3 deficiency significantly enhanced neutrophil phagocytosis, proinflammatory cytokine production, and netosis.
  • Mice lacking Dok3 exhibited increased survival rates against a lethal dose of Candida albicans.
  • Dok3 was found to recruit PP1 to dephosphorylate Card9, thereby inhibiting NF-κB and JNK activation and dampening antifungal immune responses.

Conclusions:

  • Dok3 acts as a negative regulator of innate antifungal immunity by suppressing Card9 signaling in neutrophils.
  • Targeting the Dok3-Card9 interaction or PP1 activity presents a promising therapeutic strategy for treating candidemia and other invasive fungal infections.
Keywords:
Adaptor proteinsImmunologyInfectious diseaseInnate immunity

More Related Videos

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder09:29

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

Published on: January 9, 2015

15.8K
Standardized In vitro Assays to Visualize and Quantify Interactions between Human Neutrophils and Staphylococcus aureus Biofilms07:28

Standardized In vitro Assays to Visualize and Quantify Interactions between Human Neutrophils and Staphylococcus aureus Biofilms

Published on: June 8, 2022

3.0K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.4K
Contact-dependent Signaling01:19

Contact-dependent Signaling

Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
46.9K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.1K
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.8K