Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis

Area of Science:

• Immunology
• Microbiology
• Pathogen-host interactions

Background:

• Severe infections trigger cytokine storms and immune exhaustion.
• Pathogens possess anti-inflammatory mechanisms that could be therapeutically exploited.
• Candida albicans (C. albicans) is a common human fungal pathogen.

Purpose of the Study:

• To investigate the potential of C. albicans N-glycans to ameliorate sepsis.
• To explore the underlying mechanisms of N-glycan-mediated immunosuppression.

Main Methods:

• Administered C. albicans N-glycans to a lipopolysaccharide (LPS)-induced mouse sepsis model.
• Measured serum cytokine levels (IL-10, IL-1β, TNF-α, IFN-γ).
• Assessed mouse survival rates and immune exhaustion markers.
• Utilized structurally defined N-glycans and Dectin-2 knockout mice for mechanistic studies.

Main Results:

• C. albicans N-glycans upregulated immunosuppressive IL-10 and suppressed pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ) in LPS-challenged mice.
• N-glycan administration improved survival in the sepsis model.
• The mannose core of N-glycans was crucial for IL-10 induction.
• Dectin-2 signaling mediated the N-glycan-induced IL-10 response.
• C. albicans N-glycans alleviated immune exhaustion post-inflammation.

Conclusions:

• Fungal N-glycans can mitigate sepsis and associated immune dysfunction.
• Targeting pathogen-derived immunosuppressive molecules offers a novel therapeutic strategy for severe inflammation.
• The mannose core and Dectin-2 pathway are key components of this therapeutic mechanism.