Related Experiment Video
Updated: Mar 17, 2026
Infecting Mice with Malassezia spp. to Study the Fungus-Host Interaction
Published on: November 6, 2019
Impairment of Immune Response against Dematiaceous Fungi in Card9 Knockout Mice
Weiwei Wu1,2,3, Ruijun Zhang1,2,3, Xiaowen Wang1,2,3
1Department of Dermatology, Peking University First Hospital, Beijing, China.
Abstract:
Dematiaceous fungi are a large group of pathogens that can cause a wide range of diseases in both immunocompetent and immunocompromised hosts. Based on our previous finding of caspase recruitment domain-containing protein 9 (CARD9) mutations in patients with subcutaneous phaeohyphomycosis caused by Phialophora verrucosa (P. verrucosa), we further investigated the exact role of CARD9 in the pathogenesis of phaeohyphomycosis using Card9 knockout (Card9 KO) mice. We showed that Card9 KO mice are profoundly susceptible to P. verrucosa infection compared with wild-type mice, reflected by significantly more severe footpad swelling, higher fungal burden, lower survival, and systemic dissemination. The inability of Card9 KO mice to control P. verrucosa infection was associated with lack of Th17 differentiation and reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A levels in footpad homogenates. In vitro experiments showed a defect of fungal conidia killing and pro-inflammatory cytokine production in Card9 KO bone marrow-derived macrophages and dendritic cells. Furthermore, ex vivo coculture and in vitro T cell differentiation assay demonstrated that Card9 signaling pathway acts indispensably on differentiation of Th17 cells. In conclusion, our findings suggest that CARD9 mediate the innate immune and Th17-mediated adaptive immune responses against dematiaceous fungal infections at the early stage of infection.
Insights
Caspase recruitment domain-containing protein 9 (CARD9) is crucial for controlling dematiaceous fungal infections. CARD9 deficiency impairs immune responses, leading to increased susceptibility and severity of phaeohyphomycosis.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Dematiaceous fungi cause diverse diseases in various hosts.
- Previous studies linked caspase recruitment domain-containing protein 9 (CARD9) mutations to subcutaneous phaeohyphomycosis.
Purpose of the Study:
- To investigate the role of CARD9 in the pathogenesis of phaeohyphomycosis caused by Phialophora verrucosa.
- To elucidate the mechanisms underlying CARD9-mediated immunity against dematiaceous fungi.
Main Methods:
- Utilized Card9 knockout (Card9 KO) mice for infection studies with Phialophora verrucosa.
- Assessed fungal burden, host immune cell responses (Th17 differentiation), and cytokine production (TNF-α, IL-1β, IL-6, IL-17A).
- Conducted in vitro experiments with bone marrow-derived macrophages and dendritic cells, alongside ex vivo coculture and T cell differentiation assays.
Main Results:
- Card9 KO mice exhibited increased susceptibility to P. verrucosa, with more severe swelling, higher fungal load, reduced survival, and systemic dissemination.
- Lack of Th17 cell differentiation and reduced levels of key pro-inflammatory cytokines were observed in Card9 KO mice.
- In vitro studies revealed defects in fungal conidia killing and cytokine production in Card9-deficient immune cells.
- CARD9 signaling was found to be essential for Th17 cell differentiation.
Conclusions:
- CARD9 plays a vital role in mediating both innate and adaptive immune responses against dematiaceous fungal infections.
- The CARD9 signaling pathway is indispensable for early-stage control of Phialophora verrucosa infection, particularly through Th17 cell induction.
