2 research outputs found
<i>Candida albicans</i> Modifies the Protein Composition and Size Distribution of THP-1 Macrophage-Derived Extracellular Vesicles
The effectiveness
of macrophages in the response to systemic candidiasis
is crucial to an effective clearance of the pathogen. The secretion
of proteins, mRNAs, noncoding RNAs and lipids through extracellular
vesicles (EVs) is one of the mechanisms of communication between immune
cells. EVs change their cargo to mediate different responses, and
may play a role in the response against infections. Thus we have undertaken
the first quantitative proteomic analysis on the protein composition
of THP-1 macrophage-derived EVs during the interaction with <i>Candida albicans</i>. This study revealed changes in EVs sizes
and in protein composition, and allowed the identification and quantification
of 717 proteins. Of them, 133 proteins changed their abundance due
to the interaction. The differentially abundant proteins were involved
in functions relating to immune response, signaling, or cytoskeletal
reorganization. THP-1-derived EVs, both from control and from <i>Candida</i>-infected macrophages, had similar effector functions
on other THP-1-differenciated macrophages, activating ERK and p38
kinases, and increasing both the secretion of proinflammatory cytokines
and the candidacidal activity; while in THP-1 nondifferenciated monocytes,
only EVs from infected macrophages increased significantly the TNF-α
secretion. Our findings provide new information on the role of macrophage-derived
EVs in response to <i>C. albicans</i> infection and in macrophages
communication
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