Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome.

Abstract

The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1β. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1β production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1β secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1β secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K⁺ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.

• Authors: Hua Li, Shuxian Wu, Liming Mao, Guowei Lei, Liping Zhang, Ailing Lu, Liguo An, Guiwen Yang, Paride Abliz, Guangxun Meng
• Journal: Protein & cell (Protein Cell) Vol. 4 Issue 7 Pg. 529-38 (Jul 2013) ISSN: 1674-8018 [Electronic] Germany
• PMID: 23686720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Reactive Oxygen Species
• Caspase 1
• Potassium

Topics

• Animals
• Bone Marrow Cells (cytology)
• Carrier Proteins (metabolism)
• Caspase 1 (metabolism)
• Cell Line
• Dendritic Cells (cytology, metabolism, microbiology)
• Enzyme Activation
• Hot Temperature
• Humans
• Inflammasomes (metabolism)
• Interleukin-1beta (biosynthesis, metabolism)
• Lysosomes (metabolism)
• Mice
• Monocytes (cytology, metabolism, microbiology)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Potassium (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Trichophyton (physiology)