TY - JOUR
T1 - Candida Extracellular Nucleotide Metabolism Promotes Neutrophils Extracellular Traps Escape
AU - Afonso, Mariana
AU - Mestre, Ana Rita
AU - Silva, Guilherme
AU - Almeida, Ana Catarina
AU - Cunha, Rodrigo A.
AU - Meyer-Fernandes, José Roberto
AU - Gonçalves, Teresa
AU - Rodrigues, Lisa
N1 - Funding Information:
This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0246-FEDER-000010, CENTRO-01-0145-FEDER-000012-HealthyAging2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT-Fundação para a Ciência e a Tecnologia, under projects POCI-01-0145-FEDER-007440 and UID/NEU/04539/2019.
Publisher Copyright:
© Copyright © 2021 Afonso, Mestre, Silva, Almeida, Cunha, Meyer-Fernandes, Gonçalves and Rodrigues.
PY - 2021/7/13
Y1 - 2021/7/13
N2 - Host innate immunity is fundamental to the resistance against Candida albicans and Candida glabrata infection, two of the most important agents contributing to human fungal infections. Phagocytic cells, such as neutrophils, constitute the first line of host defense mechanisms, and the release of neutrophil extracellular traps (NETs) represent an important strategy to immobilize and to kill invading microorganisms, arresting the establishment of infection. The purinergic system operates an important role in the homeostasis of immunity and inflammation, and ectophosphatase and ectonucleotidase activities are recognized as essential for survival strategies and infectious potential of several pathogens. The expression and unique activity of a 3′-nucleotidase/nuclease (3′NT/NU), able to hydrolyze not only AMP but also nucleic acids, has been considered as part of a possible mechanism of microbes to escape from NETs. The aim of the present study was to evaluate if yeasts escape from the NET-mediated killing through their 3′NT/NU enzymatic activity contributing to NET-hydrolysis. After demonstrating the presence of 3′NT/NU activity in C. albicans, C. glabrata, and Saccharomyces cerevisiae, we show that, during neutrophils-Candida interaction, when NETs formation and release are triggered, NETs digestion occurs and this process of NETs disruption promoted by yeast cells was prevented by ammonium tetrathiomolybdate (TTM), a 3′NT/NU inhibitor. In conclusion, although the exact nature and specificity of yeasts ectonucleotidases are not completely unraveled, we highlight the importance of these enzymes in the context of infection, helping yeasts to overcome host defenses, whereby C. albicans and C. glabrata can escape NET-mediate killing through their 3′NT/NU activity.
AB - Host innate immunity is fundamental to the resistance against Candida albicans and Candida glabrata infection, two of the most important agents contributing to human fungal infections. Phagocytic cells, such as neutrophils, constitute the first line of host defense mechanisms, and the release of neutrophil extracellular traps (NETs) represent an important strategy to immobilize and to kill invading microorganisms, arresting the establishment of infection. The purinergic system operates an important role in the homeostasis of immunity and inflammation, and ectophosphatase and ectonucleotidase activities are recognized as essential for survival strategies and infectious potential of several pathogens. The expression and unique activity of a 3′-nucleotidase/nuclease (3′NT/NU), able to hydrolyze not only AMP but also nucleic acids, has been considered as part of a possible mechanism of microbes to escape from NETs. The aim of the present study was to evaluate if yeasts escape from the NET-mediated killing through their 3′NT/NU enzymatic activity contributing to NET-hydrolysis. After demonstrating the presence of 3′NT/NU activity in C. albicans, C. glabrata, and Saccharomyces cerevisiae, we show that, during neutrophils-Candida interaction, when NETs formation and release are triggered, NETs digestion occurs and this process of NETs disruption promoted by yeast cells was prevented by ammonium tetrathiomolybdate (TTM), a 3′NT/NU inhibitor. In conclusion, although the exact nature and specificity of yeasts ectonucleotidases are not completely unraveled, we highlight the importance of these enzymes in the context of infection, helping yeasts to overcome host defenses, whereby C. albicans and C. glabrata can escape NET-mediate killing through their 3′NT/NU activity.
KW - Candida
KW - neutrophil extracellular traps escape
KW - neutrophils
KW - nucleotidase
KW - nucleotide metabolism
UR - http://www.scopus.com/inward/record.url?scp=85111352670&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/34327150
U2 - 10.3389/fcimb.2021.678568
DO - 10.3389/fcimb.2021.678568
M3 - Article
C2 - 34327150
AN - SCOPUS:85111352670
SN - 2235-2988
VL - 11
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 678568
ER -