16677
2016
eng
e0166648
11
11
article
1
2018-08-07
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Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans
Background
Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO).
Hypothesis
Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses.
Methods
The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor).
Results
Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO).
Conclusion
Our data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.
PLoS ONE
10.1371/journal.pone.0166648
urn:nbn:de:bvb:20-opus-166778
PLoS ONE 11(11):e0166648 (2016). DOI: 10.1371/journal.pone.0166648
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Stephan Dreschers
Peter Saupp
Mathias Hornef
Andrea Prehn
Christopher Platen
Joachim Morschhäuser
Thorsten W. Orlikowsky
eng
uncontrolled
Candida albicans
eng
uncontrolled
monocytes
eng
uncontrolled
immune response
eng
uncontrolled
PICD
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16677/Dreschers_PLoS_ONE.pdf
14827
2015
eng
764
6
article
1
2017-05-10
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Integrated inference and evaluation of host-fungi interaction networks
Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi human and fungi mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host fungi transcriptome and proteome data.
Frontiers in Microbiology
10.3389/fmicb.2015.00764
urn:nbn:de:bvb:20-opus-148278
Frontiers in Microbiology 6:764 (2015). DOI: 10.3389/fmicb.2015.00764
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Christian W. Remmele
Christian H. Luther
Johannes Balkenhol
Thomas Dandekar
Tobias Müller
Marcus T. Dittrich
eng
uncontrolled
candida genome database
eng
uncontrolled
computational prediction
eng
uncontrolled
potential role
eng
uncontrolled
network inference
eng
uncontrolled
bioinformatics and computational biology
eng
uncontrolled
protein interaction database
eng
uncontrolled
Aspergillus fumigatus
eng
uncontrolled
cell wall
eng
uncontrolled
functional modules
eng
uncontrolled
alzheimers disease
eng
uncontrolled
molecular cloning
eng
uncontrolled
Candida albicans
eng
uncontrolled
pathogen-host interaction (PHI)
eng
uncontrolled
protein-protein interaction
eng
uncontrolled
pathogenicity
eng
uncontrolled
interolog
Medizin und Gesundheit
open_access
Institut für Humangenetik
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14827/009_Remmele_Frontiers_in_Microbiology.pdf
15162
2015
eng
625
6
article
1
2017-07-17
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Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies
The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.
Frontiers in Microbiology
10.3389/fmicb.2015.00625
urn:nbn:de:bvb:20-opus-151621
Frontiers in Microbiology, 6, 625 (2015). DOI: 3389/fmicb.2015.00625
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sybille Dühring
Sebastian Germerodt
Christine Skerka
Peter F. Zipfel
Thomas Dandekar
Stefan Schuster
eng
uncontrolled
agent-based model
eng
uncontrolled
antimicrobial peptides
eng
uncontrolled
fungal pathogens
eng
uncontrolled
Candida albicans
eng
uncontrolled
immunological cross-talk
eng
uncontrolled
beta-lactamase inhibition
eng
uncontrolled
in vitro
eng
uncontrolled
biomaterial surfaces
eng
uncontrolled
biofilm formation
eng
uncontrolled
dendritic cells
eng
uncontrolled
infection
eng
uncontrolled
resistance
eng
uncontrolled
human immune system
eng
uncontrolled
host-pathogen interaction
eng
uncontrolled
computational systems biology
eng
uncontrolled
defense and evasion strategies
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15162/024_Duehring_FRONTIERS-IN-MICROBIOLOGY.pdf