Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis.
Candida albicans is a commensal fungus that can cause systemic disease in patients with breaches in mucosal integrity, indwelling catheters, and defects in phagocyte function. Although circulating human and murine monocytes bind C. albicans and promote inflammation, it remains unclear whether C-C chemokine receptor 2 (CCR2)- and Ly6C-expressing inflammatory monocytes exert a protective or a deleterious function during systemic infection. During murine systemic candidiasis, interruption of CCR2-dependent inflammatory monocyte trafficking into infected kidneys impaired fungal clearance and decreased murine survival. Depletion of CCR2-expressing cells led to uncontrolled fungal growth in the kidneys and brain and demonstrated an essential antifungal role for inflammatory monocytes and their tissue-resident derivatives in the first 48 hours postinfection. Adoptive transfer of purified inflammatory monocytes in depleted hosts reversed the defect in fungal clearance to a substantial extent, indicating a compartmentally and temporally restricted protective function that can be transferred to enhance systemic innate antifungal immunity.
Vaccine and Infectious Diseases Division.
Lisa Y
LY
Ngo
Shinji
S
Kasahara
Debra K
DK
Kumasaka
Sue E
SE
Knoblaugh
Anupam
A
Jhingran
Tobias M
TM
Hohl
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000382:microbiology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D015169:Colony Count, Microbial; D004198:Disease Susceptibility; D005838:Genotype; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D009928:Organ Specificity; D054390:Receptors, CCR2 / Q000378:metabolism; D018709:Statistics, Nonparametric
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2
CCR2; Candida; brain; candidiasis; chemokine; fungus; graft; host defense; inflammatory; innate; kidney; monocyte; mortality; renal; sepsis; transfer; yeast