Limits...
Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α-Dependent, IL-17-Independent Mechanism.

Whibley N, Jaycox JR, Reid D, Garg AV, Taylor JA, Clancy CJ, Nguyen MH, Biswas PS, McGeachy MJ, Brown GD, Gaffen SL - J. Immunol. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;

Show MeSH

Related in: MedlinePlus

Monocyte expansion and recruitment to the kidneys is not impaired in CARD9−/− mice during C. tropicalis infection. Blood (A and B) and kidneys (C) were analyzed by flow cytometry for CD45+CD11b+Ly6G−Ly6C+ monocytes at the indicated time points postinfection. Data are pooled from two to six experiments (n = 4–20 mice/time point). Cells were gated through leukocyte, single cell, live cell, and CD45+ gates. *p < 0.05, Kruskal-Wallis and post hoc Dunn multiple-comparisons tests.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4592105&req=5

fig06: Monocyte expansion and recruitment to the kidneys is not impaired in CARD9−/− mice during C. tropicalis infection. Blood (A and B) and kidneys (C) were analyzed by flow cytometry for CD45+CD11b+Ly6G−Ly6C+ monocytes at the indicated time points postinfection. Data are pooled from two to six experiments (n = 4–20 mice/time point). Cells were gated through leukocyte, single cell, live cell, and CD45+ gates. *p < 0.05, Kruskal-Wallis and post hoc Dunn multiple-comparisons tests.

Mentions: We next assessed the expansion and recruitment of monocytes in the blood and kidneys of C. tropicalis–infected mice. In contrast to neutrophil numbers, monocyte expansion in the bloodstream was not detected until day 5 in both WT and CARD9−/− mice (Fig. 6A, 6B). Similarly, an increase in monocyte numbers was only detected in the kidneys of WT and CARD9−/− mice at day 5 (Fig. 6C). No defect in monocyte expansion or recruitment was detected in the blood or kidneys in CARD9−/− mice. In fact, monocyte absolute numbers were markedly higher in the kidneys of CARD9−/− mice compared with WT mice at day 5, in line with elevated neutrophil responses (Figs. 5F, 6C). Together, these data demonstrate that CARD9−/− mice are not impaired in neutrophil and monocyte expansion and recruitment during C. tropicalis infection. Rather, CARD9 deficiency leads to heightened neutrophil and monocyte responses in the kidneys that may contribute to pathogenicity.


Delinking CARD9 and IL-17: CARD9 Protects against Candida tropicalis Infection through a TNF-α-Dependent, IL-17-Independent Mechanism.

Whibley N, Jaycox JR, Reid D, Garg AV, Taylor JA, Clancy CJ, Nguyen MH, Biswas PS, McGeachy MJ, Brown GD, Gaffen SL - J. Immunol. (2015)

Monocyte expansion and recruitment to the kidneys is not impaired in CARD9−/− mice during C. tropicalis infection. Blood (A and B) and kidneys (C) were analyzed by flow cytometry for CD45+CD11b+Ly6G−Ly6C+ monocytes at the indicated time points postinfection. Data are pooled from two to six experiments (n = 4–20 mice/time point). Cells were gated through leukocyte, single cell, live cell, and CD45+ gates. *p < 0.05, Kruskal-Wallis and post hoc Dunn multiple-comparisons tests.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592105&req=5

fig06: Monocyte expansion and recruitment to the kidneys is not impaired in CARD9−/− mice during C. tropicalis infection. Blood (A and B) and kidneys (C) were analyzed by flow cytometry for CD45+CD11b+Ly6G−Ly6C+ monocytes at the indicated time points postinfection. Data are pooled from two to six experiments (n = 4–20 mice/time point). Cells were gated through leukocyte, single cell, live cell, and CD45+ gates. *p < 0.05, Kruskal-Wallis and post hoc Dunn multiple-comparisons tests.
Mentions: We next assessed the expansion and recruitment of monocytes in the blood and kidneys of C. tropicalis–infected mice. In contrast to neutrophil numbers, monocyte expansion in the bloodstream was not detected until day 5 in both WT and CARD9−/− mice (Fig. 6A, 6B). Similarly, an increase in monocyte numbers was only detected in the kidneys of WT and CARD9−/− mice at day 5 (Fig. 6C). No defect in monocyte expansion or recruitment was detected in the blood or kidneys in CARD9−/− mice. In fact, monocyte absolute numbers were markedly higher in the kidneys of CARD9−/− mice compared with WT mice at day 5, in line with elevated neutrophil responses (Figs. 5F, 6C). Together, these data demonstrate that CARD9−/− mice are not impaired in neutrophil and monocyte expansion and recruitment during C. tropicalis infection. Rather, CARD9 deficiency leads to heightened neutrophil and monocyte responses in the kidneys that may contribute to pathogenicity.

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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;

Show MeSH
Related in: MedlinePlus