Genetic variation of innate immune genes in HIV-infected african patients with or without oropharyngeal candidiasis.
BACKGROUND
The occurrence of oropharyngeal candidiasis (OPC) in combination with HIV disease progression is a very common phenomenon. However, not all HIV-infected patients develop OPC, even when they progress to low CD4 T-cell counts. Because T-cell immunity is defective in AIDS, the innate defence mechanisms are likely to have a central role in antifungal immunity in these patients. We investigated whether genetic variations in the innate immune genes DECTIN-1, TLR2, TLR4, TIRAP, and CASPASE-12 are associated with the presence of OPC in HIV-infected subjects from East Africa.


METHODS
A total of 225 HIV patients were genotyped for several single nucleotide polymorphisms (SNPs), and this was correlated with the occurrence of OPC in these patients. In addition, primary immune cells obtained from individuals with different genotypes were stimulated with Candida albicans, and cytokine production was measured.


RESULTS
The analysis revealed that no significant differences in the polymorphism frequencies could be observed, although a tendency toward a protective effect on OPC of the DECTIN-1 I223S SNP was apparent. Furthermore, interferon gamma production capacity was markedly lower in cells bearing the DECTIN-1 SNP I223S. It could also be demonstrated that the 223S mutated form of the DECTIN-1 gene exhibits a lower capacity to bind zymosan.


CONCLUSIONS
These data demonstrate that common polymorphisms of TLR2, TLR4, TIRAP, and CASPASE-12 do not influence susceptibility to OPC in HIV-infected patients in East Africa but suggest an immunomodulatory effect of the I223S SNP on dectin-1 function and possibly the susceptibility to OPC in HIV patients.
Plantinga
Theo S
TS
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hamza
Omar J M
OJ
Willment
Janet A
JA
Ferwerda
Bart
B
van de Geer
Nicole M D
NM
Verweij
Paul E
PE
Matee
Mecky I N
MI
Banahan
Kathy
K
O'neill
Luke A J
LA
Kullberg
Bart-Jan
BJ
Brown
Gordon D
GD
van der Ven
André J A M
AJ
Netea
Mihai G
MG
D000349:Africa; D002176:Candida albicans / Q000276:immunology / Q000302:isolation & purification; D002180:Candidiasis, Oral / Q000453:epidemiology* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005800:Genes, Fungal; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology
D016207:Cytokines