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

Yi Juan Teo,Sajith Kumar Nair,Jianpeng Sheng,Qi Chen,Keng Wai Mak,Christiane Ruedl,See Liang Ng,Yolanda Aphrilia Setiagani

doi:10.26508/lsa.202000890

Abstract

Disseminated candidiasis remains as the most common hospital-acquired bloodstream fungal infection with up to 40% mortality rate despite the advancement of medical and hygienic practices. While it is well established that this infection heavily relies on the innate immune response for host survival, much less is known for the protective role elicited by the tissue-resident macrophage (TRM) subsets in the kidney, the prime organ for Candida persistence. Here, we describe a unique CD169++ TRM subset that controls Candida growth and inflammation during acute systemic candidiasis. Their absence causes severe fungal-mediated renal pathology. CD169++ TRMs, without being actively involved in direct fungal clearance, increase host resistance by promoting IFN-γ release and neutrophil ROS activity.

Highlights

Systemic candidiasis is the fourth common bloodstream nosocomial infection that was estimated to affect more than 250,000 intensive care unit patients every year, despite the administration of hygienic practices in the hospitals (Delaloye & Calandra, 2014; Kullberg & Arendrup, 2015)
Based on the ablated and unablated tissue-resident macrophage (TRM), we broadly subcategorized them into Fraction I (Fr I) (CD169++ F4/80++ CD11b+) and Fraction II (Fr II) (CD169+ F4/80+++ CD11b++) populations (Fig 1A and B)
The TRM ablation profile in CD169-DTR mouse is consistent with the CD169 transcript expression, wherein Fr I population express significantly higher level of CD169 as compared with Fr II population (Fig 1D)

Summary

Introduction

Systemic candidiasis is the fourth common bloodstream nosocomial infection that was estimated to affect more than 250,000 intensive care unit patients every year, despite the administration of hygienic practices in the hospitals (Delaloye & Calandra, 2014; Kullberg & Arendrup, 2015). Current treatment of this infection mainly uses antifungal drugs, the mortality rate among patients remains alarmingly high (40–60%) (Delaloye & Calandra, 2014; Bassetti et al, 2018; Lamoth et al, 2018). Much less is known in the roles of different mononuclear phagocytes in this infection in vivo, in part owing to the lack of available tools in delineating the different macrophages and dendritic cells subsets in the kidneys, which are the main target organs of systemic candidiasis (Schraml et al, 2013; Gottschalk & Kurts, 2015)

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Results

Conclusion