An integrated model of the recognition of Candida albi-cans 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. albi-cans)?• Non-pathogen vs Pathogen
– Often colonization w/o causing disease– Host defence ↓ ⇒ Become a pathogen
• Different forms of Candida albicans
World J Biol Chem. Feb 26 (2010).
SAP : Secreted as-partyl pro-teases (Saps) encoding gene
Nat Rev Immunol. Jan 4 (2004).
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 immu-
nity.
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)
Class Receptors Recognition
TLRs
TLR 2 PhospholipomannanTLR 4 O-linked mannansTLR 6 ZymosanTLR 9 Fungal DNA
CLRs Dectin 1 β-glucansMannose receptor (MR), DC-SIGN N-linked mannans
NLRs
RIG 1 recep-tor
Nucleotide-binding oligomerization (NOD)-like receptors (NLRs).Retinoic-acid inducible gene 1 (RIG 1).
Bacterial peptidoglycans, Viral nucleic acid,
Not Fungi
◎ The recognition of components by pattern recognition recep-tors (PRRs)
◎ The PRRs structure representing by two domainsDomain Examples
Extracellular pathogen -recogni-tion domain
Leu-rich repeat (LRR) domain in TLRsC-type lectin domain (CLD) in CLRs
Intracellular sig-nalling domain
TLR-interleukin 1 receptor (TIR) domain in TLRsImmunoreceptor 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
Figure 2. Cell populations and pattern-recognition
receptors involved in Candida albicans recognition.
◎ Monocytes : TLRs > LRs (Lectin receptors)
◎ Macrophages : TLRs ≤ LRs
◎ Dendritic cells : Most of the PRRs
◎ Neutrphils : TLRs ≤ PRs (Phago-cytic receptors)
◎ T cells : TLRs
6. Recognition of C. albicans com-ponents
• 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 par-
ticles.– 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 re-sponse using pattern-recognition receptors.
9. ConclusionsThere are several principles that characterize
recognitionof 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 de-pends on
the mosaic of PRRs and receptor complexes.
Thank you~! Any Questions ?
