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Updated: Dec 8, 2025
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Malassezia spp. induce inflammatory cytokines and activate NLRP3 inflammasomes in phagocytes
Andrea J Wolf1, Jose J Limon1, Christopher Nguyen1
1Department of Biomedical Sciences and the Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract:
Malassezia spp. are common eukaryotic yeasts that colonize mammalian skin. Recently, the authors and others have observed that Malassezia globosa and Malassezia restricta can be found in the intestines in the context of certain diseases, including Crohn's disease and pancreatic cancer. In order to better understand the nature of innate inflammatory responses to these yeasts, inflammatory responses induced by M. restricta and M. globosa in mouse bone marrow-derived Mϕs (BMDM) and dendritic cells (BMDC) are evaluated. While Malassezia yeasts induce proinflammatory cytokine production from both Mϕs and dendritic cells, the levels of production from BMDC were more pronounced. Both M. restricta and M. globosa activated inflammatory cytokine production from BMDC in large part through Dectin2 and CARD9 signaling, although additional receptors appear to be involved in phagocytosis and activation of reactive oxygen production in response to the yeasts. Both M. restricta and M. globosa stimulate production of pro-IL-1β as well as activation of the NLRP3 inflammasome. NLRP3 inflammasome activation by Malassezia fungi requires SYK signaling, potassium efflux and actin rearrangement. Together, the data further the understanding of the coordinated involvement of multiple innate immune receptors in recognizing Malassezia globosa and Malassezia restricta and orchestrating phagocyte inflammatory and antimicrobial responses.
Insights
Malassezia yeasts, commonly found on skin, can trigger inflammatory responses in the gut. This study reveals how immune cells like dendritic cells recognize these fungi, involving key signaling pathways for an effective immune response.
Area of Science:
- Immunology
- Microbiology
- Mycology
Background:
- Malassezia yeasts (M. globosa, M. restricta) commonly colonize mammalian skin.
- These yeasts are increasingly found in the gut during diseases like Crohn's disease and pancreatic cancer.
- Understanding innate immune responses to Malassezia is crucial for disease pathogenesis.
Purpose of the Study:
- To investigate the innate inflammatory responses induced by Malassezia globosa and Malassezia restricta.
- To elucidate the signaling pathways and immune receptors involved in recognizing these yeasts by phagocytes.
Main Methods:
- Utilized mouse bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC).
- Assessed inflammatory cytokine production, inflammasome activation (NLRP3), and signaling pathways (Dectin2, CARD9, SYK).
- Investigated the roles of potassium efflux and actin rearrangement in NLRP3 inflammasome activation.
Main Results:
- Malassezia yeasts induced pro-inflammatory cytokine production from both BMDM and BMDC, with higher levels from BMDC.
- Dectin2 and CARD9 signaling were critical for Malassezia-induced cytokine production in BMDC.
- NLRP3 inflammasome activation by Malassezia required SYK signaling, potassium efflux, and actin rearrangement.
Conclusions:
- Malassezia yeasts engage multiple innate immune receptors for recognition and response.
- The study enhances understanding of the coordinated immune mechanisms against Malassezia.
- These findings contribute to understanding the role of Malassezia in inflammatory conditions.
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