Phagocytes from Mice Lacking the Sts Phosphatases Have an Enhanced Antifungal Response to Candida albicans

MBio
David M FrankNick Carpino

Abstract

Mice lacking expression of the homologous phosphatases Sts-1 and Sts-2 (Sts-/- mice) are resistant to disseminated candidiasis caused by the fungal pathogen Candida albicans To better understand the immunological mechanisms underlying the enhanced resistance of Sts-/- mice, we examined the kinetics of fungal clearance at early time points. In contrast to the rapid C. albicans growth seen in normal kidneys during the first 24 h postinfection, we observed a reduction in kidney fungal CFU within Sts-/- mice beginning at 12 to 18 h postinfection. This corresponds to the time period when large numbers of innate leukocytes enter the renal environment to counter the infection. Because phagocytes of the innate immune system are important for host protection against pathogenic fungi, we evaluated responses of bone marrow leukocytes. Relative to wild-type cells, Sts-/- marrow monocytes and bone marrow-derived dendritic cells (BMDCs) displayed a heightened ability to inhibit C. albicans growth ex vivo This correlated with significantly enhanced production of reactive oxygen species (ROS) by Sts-/- BMDCs downstream of Dectin-1, a C-type lectin receptor that plays a critical role in stimulating host responses to fungi. We observed no visibl...Continue Reading

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Methods Mentioned

BETA
flow cytometry
PMA
fluorescence-activated cell sorter
enzyme-linked immunosorbent assay

Software Mentioned

SigmaPlot
Softmax Pro

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