Renal CD169⁺⁺ resident macrophages are crucial for protection against acute systemic candidiasis

Area of Science:

• Immunology
• Mycology
• Infectious Diseases

Background:

• Disseminated candidiasis is a common hospital-acquired fungal infection with high mortality.
• The innate immune response is critical for survival, but the role of kidney-resident macrophages is poorly understood.
• The kidney is a primary site for Candida persistence during systemic infection.

Purpose of the Study:

• To identify and characterize specific tissue-resident macrophage (TRM) subsets in the kidney that influence host defense against disseminated candidiasis.
• To elucidate the protective mechanisms employed by these TRMs during acute systemic fungal infection.

Main Methods:

• Flow cytometry and cell surface marker analysis to identify unique TRM subsets in the kidney.
• Experimental models of acute systemic candidiasis to assess the role of CD169++ TRMs.
• Measurement of fungal burden, inflammatory markers (e.g., IFN-γ), and neutrophil activity (e.g., ROS).

Main Results:

• Identification of a distinct CD169++ TRM subset in the kidney.
• Absence of CD169++ TRMs resulted in exacerbated fungal growth and severe renal pathology.
• CD169++ TRMs enhanced host resistance by promoting IFN-γ release and neutrophil reactive oxygen species (ROS) activity, without direct fungal clearance.

Conclusions:

• CD169++ TRMs play a critical role in controlling fungal growth and inflammation in the kidney during disseminated candidiasis.
• These macrophages are essential for mitigating renal pathology and improving host survival by modulating the innate immune response.
• Targeting CD169++ TRMs may offer a novel therapeutic strategy for invasive fungal infections.