Apoptosis of Candida albicans during the Interaction with Murine Macrophages: Proteomics and Cell-Death Marker Monitoring

Macrophages
may induce fungal apoptosis to fight against C. albicans, as previously hypothesized by our group.
To confirm this hypothesis, we analyzed proteins from C. albicans cells after 3 h of interaction with macrophages
using two quantitative proteomic approaches. A total of 51 and 97
proteins were identified as differentially expressed by DIGE and iTRAQ,
respectively. The proteins identified and quantified were different,
with only seven in common, but classified in the same functional categories.
The analyses of their functions indicated that an increase in the
metabolism of amino acids and purine nucleotides were taking place,
while the glycolysis and translation levels dropped after 3 h of interaction.
Also, the response to oxidative stress and protein translation were
reduced. In addition, seven substrates of metacaspase (Mca1) were
identified (Cdc48, Fba1, Gpm1, Pmm1, Rct1, Ssb1, and Tal1) as decreased
in abundance, plus 12 proteins previously described as related to
apoptosis. Besides, the monitoring of apoptotic markers along 24 h
of interaction (caspase-like activity, TUNEL assay, and the measurement
of ROS and cell examination by transmission electron microscopy) revealed
that apoptotic processes took place for 30% of the fungal cells, thus
supporting the proteomic results and the hypothesis of macrophages
killing C. albicans by apoptosis.