Transcript An integrated model of the recognition of Candida albicans

An integrated model of the
recognition of Candida albicans
by the innate immune system
Nature Reviews / Microbiology
Volume 6 / January 2008
Lab of Biochemistry, Korea University
Division of Influenza Virus, National Institute of Health, KCDC
Shin Kyeongcheol / 2010. 4. 28
1. Candida albicans (C. albicans)?
• Non-pathogen vs Pathogen
– Often colonization w/o causing disease
– Host defence ↓ ⇒ Become a pathogen
• Different forms of Candida albicans
SAP :
Secreted aspartyl
proteases (Saps)
encoding gene
Nat Rev Immunol. Jan 4 (2004).
World J Biol Chem. Feb 26 (2010).
2. Innate immunity and host defence
• Major player : Neutrophil, Macrophage
• Innate immunity had been performed only simple
‘ingest and destroy’ tasks.
– How recognize?
– Why different responses?
• Recently, it becomes clear.
– PRRs recognize PAMPs.
– PRRs initiate and modulate subsequent adaptive immunity.
3. Pattern recognition recepters (PRRs)
• PRRs sense conserved chemical signatures callded
pathogen-assosiated molecular patterns (PAMPs).
• 4 major classes of PRRs
– Toll-like receptors (TLRs)
• Cell membrane associated and intracellular receptors
• Recognition of fungal components
– C-type lectin receptors (CLRs)
• Membrane-bound receptors
• Recognition of polysaccharide structures from Candida albicans
– NLRs and RIG1 receptors
• Intracellular receptors
• Recognition of Bacterial peptidoglycans and viral nucleic acids, not fungi
– PRRs = Extracellular pathogen-recognition domain
+ Intracellular signaling domain
3. Pattern recognition recepters (PRRs)
◎ The recognition of components by pattern recognition receptors (PRRs)
Class
Receptors
Recognition
TLR 2
Phospholipomannan
TLR 4
O-linked mannans
TLR 6
Zymosan
TLR 9
Fungal DNA
Dectin 1
β-glucans
Mannose receptor (MR), DC-SIGN
N-linked mannans
TLRs
CLRs
NLRs
RIG 1 receptor
Nucleotide-binding oligomerization
(NOD)-like receptors (NLRs).
Retinoic-acid inducible gene 1 (RIG 1).
Bacterial peptidoglycans,
Viral nucleic acid,
Not Fungi
◎ The PRRs structure representing by two domains
Domain
Examples
Extracellular pathogen recognition domain
Leu-rich repeat (LRR) domain in TLRs
Intracellular signalling
domain
C-type lectin domain (CLD) in CLRs
TLR-interleukin 1 receptor (TIR) domain in TLRs
Immunoreceptor Tyr-based activation-like motif (ITAM) in CLRs
4. The C. albicans cell wall
Figure 1. The structure of the Candida albicans cell wall.
5. Immune cells for C. albicans recognition
◎ Monocytes
: TLRs > LRs (Lectin
receptors)
◎ Macrophages
: TLRs ≤ LRs
◎ Dendritic cells
: Most of the PRRs
◎ Neutrphils
: TLRs ≤ PRs (Phagocytic
receptors)
Figure 2. Cell populations and pattern-recognition
receptors involved in Candida albicans recognition.
◎ T cells
: TLRs
6. Recognition of C. albicans components
• Mannans and mannoproteins
– Localization in the outermost part of the cell wall.
– Immunostimulatory activities.
– Recognition mainly by MR, DC-SIGN and TLR4.
• β-glucans
–
–
–
–
60% of cell wall components.
Recognize restriction region, such as bud scars.
Recognition mainly by CR3 and Dectin 1.
Phagocytosis by neutrophils mediated β-(1,6)-glucans.
• Other C. albicans components
– Chitin : Induces recruitment of immune cells.
– Fungal DNA : Recognition of non-self DNA by TLR9.
7. Activation of host defence by PRRs
• C. albicans uptake
– Dectin 1, MR and DC-SIGN mediate directly to uptake of fungal particles.
– TLRs : Subsequent maturation of the phagosome, presentation of Ag.
• C. albicans killing
– Dectin 1 induces the respiratory burst.
– Respiratory burst
: production of toxic oxydants, activation of granule protease.
• Cytokine production
7. Activation of host defence by PRRs
Figure 3. Recognition of Candida albicans at the membrane level.
8. Escape mechanisms based on PRRs
Figure 4. Candida albicans mechanisms to escape the innate response using
pattern-recognition receptors.
9. Conclusions
There are several principles that characterize recognition
of Candida albicans.
1. Recognition depend on several PAMPs in the fungal cell wall.
2. Specific intracellular signalling pathways, and distinct consequences
for the host immune response.
3. Cell-type-specific response of the various PRRs.
4. The fully integrated response to a specific pathogen depends on
the mosaic of PRRs and receptor complexes.
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