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
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Mentions: TNF-α enhances neutrophil killing of C. albicans and C. glabrata (56, 58), but its effects on C. tropicalis have not been investigated. To test the hypothesis that CARD9-induced TNF-α augments neutrophil killing of C. tropicalis, bone marrow–derived neutrophils from WT or CARD9−/− mice were incubated with this fungus in the presence or absence of TNF-α, and the neutrophil-killing capacity of C. tropicalis was determined by measuring CFU. Incubation with TNF-α significantly enhanced the killing of C. tropicalis by both WT and CARD9−/− neutrophils (Fig. 7A), demonstrating that TNF-α augments neutrophil killing of C. tropicalis. Furthermore, WT and CARD9−/− neutrophils killed C. tropicalis equivalently (Fig. 7A). Thus, CARD9−/− neutrophils are not intrinsically defective in C. tropicalis killing and can respond to exogenous TNF-α to augment their killing activity.
Affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;