Cytokine Production by a Human Endothelial Cellline in Response to Candida Albicans
Candida albicans is the most common aetiological agent that causes haematogenously disseminated candidiasis. Under conditions that compromise the host immune system, C. albicans disseminates from mucosal sites and results in a progressive disease associated with high rates of mortality. Cytokines...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2005
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/6361/1/FPSK%28M%29_2005_20.pdf |
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| Summary: | Candida albicans is the most common aetiological agent that causes haematogenously
disseminated candidiasis. Under conditions that compromise the host immune system, C.
albicans disseminates from mucosal sites and results in a progressive disease associated
with high rates of mortality. Cytokines are important immunomodulators in coordinating
the host defense against C. albicans infection. Human endothelial cells are known to
produce various types of cytokines in response to pathogen invasion. The present study
was undertaken to identify the cytokines that are involved in the host defense against C.
albicans, as well as, to determine the importance of direct cell-to-cell contact in
triggering expression of cytokines. In addition, the involvement of Toll-like receptor
(TLR)2, TLR4 and nuclear factor-& (NF-KB) in the host defense against C. albicans
were also examined. Expression of cytokines by endothelial cells in response to C.
albicans was investigated by using an in vitro model of human umbilical vein
endothelial cell line (HUVEC) co-cultured with Candida spp. Both conventional and
real time PCR showed that among the cytokines studied, only granulocyte-macrophage
colony-stimulating factor (GM-CSF) was found to be differentially expressed in
HUVEC upon stimulation with C. albicans. Elevated levels of GM-CSF were found in
the co-culture of HUVEC with C. albicans but not in the other non-albicans Candida
spp. Three additional C. albicans strains co-cultured with HUVEC also showed a similar
pattern of increased GM-CSF expression, although at different levels from strain to
strain. This provided evidence that the induction of GM-CSF was not confined to only a
particular clinical strain of C. albicans. On the other hand, C. dubliniensis, which
possessed a similar phenotype as C. albicans failed to stimulate a similar pattern of GMCSF
expression in HUVEC. The induction of GM-CSF was then found to be contactdependent
via the use of cell culture insert to physically separate C. albicans from
adhering to the HUVEC monolayer. Pretreatment with anti-TLR2 and anti-TLR4
antibodies showed that TLR4 but not TLR2 was involved in the induction of GM-CSF
expression by HUVEC. In addition, pretreatment with SN50 inhibitor also demonstrated
that NF-KB may be involved in stimulating expression of GM-CSF transcript. In
conclusion, we have discovered that HUVEC is involved in the innate immune response
to C. albicans by producing GM-CSF cytokine through the activation of TLR4 and also
NF-KB transcription factor in a contact-dependent manner. |
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