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Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection
Aiysha Thompson1,2, Diogo M da Fonseca1,3, Louise Walker4
1Division of Infection and Immunity, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, United Kingdom.
Abstract:
More than 95% of invasive Candida infections are caused by four Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses to C. albicans. Dectin-1 promotes clearance of C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the different Candida spp. Dectin-2 is important for host immunity to C. albicans and C. glabrata, and Mincle is important for the immune response to C. albicans. However, whether Dectin-2 drives host immunity to C. tropicalis or C. parapsilosis, and whether Mincle mediates host immunity to C. glabrata, C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these four Candida spp. We demonstrate that these four Candida spp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these four Candida spp. and Dectin-2 is also important for clearance of all four Candida spp. during systemic infection. However, Mincle was only important for clearance of C. tropicalis during systemic infection. Our data indicate that multiple Candida spp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between different Candida spp. during systemic infection.
Insights
Immune responses to Candida infections depend on C-type lectin-like receptors (CLRs). Dectin-2 and Mincle play key roles in cytokine production and clearance of four Candida species, with varying importance for each species.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Invasive Candida infections are primarily caused by four species: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis.
- C-type lectin-like receptors (CLRs), including Dectin-1, Dectin-2, and Mincle, are crucial for mediating immune responses against Candida species, particularly C. albicans.
Purpose of the Study:
- To investigate the roles of Dectin-2 and Mincle in host immunity against four common Candida species.
- To determine if Dectin-2 and Mincle mediate immune responses to C. tropicalis and C. parapsilosis, and C. glabrata, C. tropicalis, and C. parapsilosis, respectively.
Main Methods:
- Comparative analysis of immune responses to four Candida species.
- Assessment of differential mannan content in Candida cell walls.
- Evaluation of cytokine production and fungal clearance during systemic infection.
Main Results:
- Candida species exhibit differential mannan content in their cell walls.
- Mincle and Dectin-2 significantly regulate cytokine production in response to all four Candida species.
- Dectin-2 is essential for clearing all four Candida species during systemic infection, while Mincle is only critical for C. tropicalis clearance.
Conclusions:
- The mannan content varies across different Candida species.
- Host immune responses to Candida infections involve differential recognition of mannan by CLRs like Mincle and Dectin-2.
- Dependence on Mincle and Dectin-2 for fungal clearance during systemic infection varies among Candida species.
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