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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration
Jessica C Hargarten1, Tyler C Moore1, Thomas M Petro2
1School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, USA.
Abstract:
The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant(s). We report here a physiological mechanism that contributes to the differences in the interaction of C. albicans white and opaque cells with macrophages. E,E-Farnesol, which is secreted by white cells only, is a potent stimulator of macrophage chemokinesis, whose activity is enhanced by yeast cell wall components and aromatic alcohols. E,E-farnesol results in up to an 8.5-fold increase in macrophage migration in vitro and promotes a 3-fold increase in the peritoneal infiltration of macrophages in vivo. Therefore, modulation of farnesol secretion to stimulate host immune recognition by macrophages may help explain why this commensal is such a successful pathogen.
Insights
Candida albicans white cells secrete E,E-farnesol, a compound that attracts macrophages. This mechanism helps the fungus evade immune destruction, contributing to its success as a pathogen.
Area of Science:
- Mycology
- Immunology
- Pathogenesis
Background:
- Candida albicans is a polymorphic fungus causing severe infections in immunocompromised individuals.
- This fungus employs immune evasion strategies, interacting with macrophages in a way that promotes its survival and pathogenesis.
- Distinct cell forms (white and opaque) exhibit different interactions with host immune cells.
Purpose of the Study:
- To elucidate the physiological mechanism behind the differential interaction of Candida albicans white and opaque cells with macrophages.
- To identify the specific molecule secreted by white cells that influences macrophage behavior.
Main Methods:
- Investigated the secretion products of C. albicans white and opaque cells.
- Assayed the effect of secreted molecules on macrophage migration (chemokinesis) in vitro.
- Evaluated the in vivo effect of the identified molecule on macrophage infiltration into the peritoneal cavity.
Main Results:
- E,E-farnesol is exclusively secreted by C. albicans white cells.
- E,E-farnesol significantly stimulates macrophage chemokinesis, increasing migration up to 8.5-fold in vitro.
- E,E-farnesol promotes a 3-fold increase in peritoneal macrophage infiltration in vivo.
- Activity of E,E-farnesol is enhanced by yeast cell wall components and aromatic alcohols.
Conclusions:
- E,E-farnesol secretion by white cells is a key mechanism for C. albicans to modulate host immune response.
- This farnesol-mediated stimulation of macrophage migration may explain the commensal's success as a pathogen.
- Targeting farnesol secretion could be a strategy to enhance host immune recognition and combat C. albicans infections.

