The role of pattern recognition receptors in the innate recognition of Candida albicans

Figures & data

Table 1. Pattern recognition receptors and C. albicans PAMPs

Family	Receptor	PAMP	References
TLRs	TLR2	Phospholipomannan	[23]
	TLR4	O-linked mannans	[24]
	TLR7	Single-stranded RNA	[26,27]
	TLR9	CpG DNA	[25]
CLRs	Dectin-1	β-(1,3)-glucan	[28]
	Dectin-2	High-mannose structures	[110-112]
	Dectin-3/Dectin-2	α-mannan	[29]
	Mannose receptor	N-linked mannan	[24]
	MINCLE	α-mannan	[114]
	Galectin-3	β-(1,2)-mannosides	[107,108]
	DC-SIGN	N-linked mannan	[151]
NLRs	NLRP3	β-glucan	[35]
	NLRC4	Unknown	[39]
	NLRP10	Unknown	[38]
Others	Mannose-binding lectin	Mannan	[30]
	SCARF1	β-glucan	[121]
	CD36	β-glucan	[121]
	Complement Receptor 3	β-(1,3)-glucan	[116]

Figure 1. Overview of PRRs for C. albicans recognition. Recognition of C. albicans is mainly mediated by Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). (A) The recognition of C. albicans by some CLRs can stimulate receptor phosphorylation and recruitment of the spleen tyrosine kinase (SYK). The association of dectin-1 with SYK activates assembly of the CARD complex (CARD9, BCL-10 and MALT-1). This results in the release of NF-κB. Syk activation also induces the noncanonical NF-κB pathway mediated by NF-κB-inducing kinase (NIK). Only the Dectin-1 and DC-SIGN recruit Ras for signal transducing, which leads to the release of NF-κB. Dectin-1 recognition of C. albicans can also activate the NLRP3 inflammasome through a mechanism that involves Syk and ROS. (B) The recognition of C. albicans by some TLRs can stimulate MyD88-dependent or TRIF-dependent pathways, leading to the release of NF-κB or the activation of IRF3/7.

Table 2. Comparision of PRR-deficient mice and human PRRs genetic polymorphisms

in-vivo mice models				polymorphisms in humans
Gene	Genotype	Effect	Reference	SNPs or haplotypes	Effect	Reference
TLR1	−/−	Unknown	/	R80T, S248N, I602S	Significantly increased susceptibility to candidemia in whites; decreased secretion of IL-1β, IL-6, and IL-8 from PBMCs of volunteers with polymorphisms	[195]
TLR2	−/−	Decreased production of TNF-α and chemokines; influence fungal clearance	[179-182]	P631H	No associations with susceptibility to candidemia; Increased susceptibility to RVVC; decreased secretion of IFN-γ and IL-17, while no influence on secretion of IL-1β, IL-6, and TNF-α from PBMCs of volunteers with polymorphisms	[195,197]
TLR3	−/−	Unknown	/	L412F	Increased prevalence of chronic candidiasis; decreased secretion of IFN-γ and TNF-α from PBMCs of volunteers with polymorphisms	[196]
TLR4	−/−	Susceptibility to candidiasis varies depending on C. albicans strains and infection routes	[182–183]	A299G	No associations with susceptibility to RVVC
No associations with susceptibility to candidemia		[197,198]
TLR6	−/−	Unknown	/	S249P	No associations with susceptibility to candidemia	[195]
TLR7	−/−	Increase susceptibility to systemic candidiasis by low doses C. albicans	[27]	Unknown	Unknown	/
TLR9	−/−	Increase susceptibility to systemic candidiasis by low doses C. albicans	[25,27]	Promoter	No associations with susceptibility to candidemia	[195]
Dectin-1	−/−	Impairement of cytokine release, phagocyte recruitment, phagocytosis and microbial killing to candidaisis	[184]	Y238X	Increased susceptibility to mucocutaneous fungal infections (like RVVC); decreased secretion of IL-17, TNF-α, IL-6 from PBMCs of volunteers with polymorphisms	[198]
Dectin-3	−/−	Increase susceptibility to systemic candidiasis by low doses C. albicans	[29]	Unknown	Unknown	/
MR	−/−	No significant difference in susceptibility to systemic candidiasis	[179]	Unknown	Unknown	/
Galectin-3	−/−	Increase susceptibility to systemic candidiasis	[186]	Unknown	Unknown	/
NLRP3	−/−	Increase susceptibility to systemic candidiasis	[36]	Unknown	Unknown	/
NLRP10	−/−	Increase susceptibility to systemic candidiasis	[38]	Unknown	Unknown	/
MyD88	−/−	Increase susceptibility to systemic candidiasis	[188]	Promoter, 3'UTR	No associations with susceptibility to candidemia	[195]
CARD9	−/−	Increase susceptibility to systemic candidiasis	[53]	S12A, Q295X	No associations with susceptibility to RVVC (S12A); Increase susceptibility to chronic mucocutaneous candidiasis (Q295X); decreased proportion of Th17 cells in RVVC patients with mutated (Q295X) CARD9	[198,170]