Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α-Dependent, IL-17-Independent Mechanism.
Bottom Line: Consistently, WT mice depleted of TNF-α were more susceptible to C. tropicalis, and CARD9-deficient neutrophils and monocytes failed to produce TNF-α following stimulation with C. tropicalis Ags.However, TNF-α treatment of neutrophils in vitro enhanced their ability to kill C. tropicalis.Moreover, CARD9-dependent production of TNF-α enhances the candidacidal capacity of neutrophils, limiting fungal disease during disseminated C. tropicalis infection.
Affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;Show MeSH
Related in: MedlinePlus
Mentions: To determine whether CARD9 is required for protection against disseminated C. tropicalis infection, WT and CARD9−/− mice were infected i.v. with 1 × 104 CFU/g C. tropicalis yeast cells, and survival and fungal burden were assessed. With this infective dose, ∼40% mortality was observed in WT mice at day 28 postinfection (Fig. 1A). In contrast, CARD9−/− mice infected with C. tropicalis showed 100% mortality by day 10 postinfection, a time point at which all WT mice remained alive (Fig. 1A). Consistent with their early mortality, CARD9−/− mice exhibited higher fungal burdens in visceral organs (kidneys, brain, and liver) than did WT mice, which was measured at day 5 when all mice were still viable (Fig. 1B). There was no difference in CFU in spleens of WT and CARD9−/− mice (Fig. 1B), suggesting tissue-specific differences in C. tropicalis infection.
Affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;