Table 2.

Summary of human studies to elucidate the role of PRRs in the development of T1D

PRR	Experimental subjects	Main findings	References
TLR
TLR2	PBMC from T1D patients and healthy controls in USA	Increased TLR2 expression in monocytes	[70]
TLR3	Pancreata from patients with fulminant diabetes in Japan	Confirmation of TLR3 expression in islet-infiltrating mononuclear cells	[56]
	Pancreata from human donors from Sweden or Finland infected with Coxsackie B5 virus or challenged with IFNα or IFN-γ with IL-1β	Enhanced expression of TLR3	[58,59]
	T1D patients and control subjects were recruited from South Africa, UK, Finland or Brazil respectively for the polymorphism screening	Significant association of SNP in theTLR3 pathways or polymorphism of the TLR3 gene with T1D.	[43,60-62]
	T1D patients and control objects were recruited from Poland or Norway respectively to test for polymorphism screening	No significant association of TLR3 polymorphism with T1D	[63,64]
TLR4	PBMC from T1D patients and healthy control subjects in the USA	Increased TLR4 expression in monocytes	[70]
	Isolated human islets obtained from non-diabetic brain-dead donors	TLR4 mRNA and surface expression were restricted to β-cells	[72]
TLR7 and TLR8	DNA samples from the sib-pair families of two parents and two affected offspring from Asia Pacific, North America and Europe.	A significant association was observed between the Xp22 SNP (rs5979785) and T1D where the Xp22 SNP is located 30 kb centromeric of the functional candidate TLR8 and TLR7 genes	[99]
TLR9	PBMC from T1D patients, their first-degree relatives and healthy controls in Czech Republic	Stimulation with CpG 2216 induced IFN-α production that was highest in relatives of T1D patients, with the exception of autoantibody-negative relatives bearing the protective haplotypes.	[89]
NLR
NLRP3	Genomic DNAs extracted from PBMCs from 196 Brazilian children and adolescents with T1D, 59 with CD, and 165 with AD.	NLRP3 rs10754558 SNP was significantly associated with T1D	[114]