Association of a NOD2 gene polymorphism and Th17 lymphocytes with presumed ocular toxoplasmosis

J Infect Dis. 2012 Oct 24. [Epub ahead of print]

Association of a NOD2 gene polymorphism and Th17 lymphocytes with presumed ocular toxoplasmosis

Dutra MS, Béla SR, Peixoto-Rangel AL, Fakiola M, Cruz AG, Gazzinelli A, Quites HF, Bahia-Oliveira LM, Peixe RG, Campos WR, Higino-Rocha AC, Miller NE, Blackwell JM, Antonelli LR, Gazzinelli RT.

Centro de Pesquisas René Rachou, CPqRR - Fundação Oswaldo Cruz, FIOCRUZ, Avenida Augusto de Lima 1517, Belo Horizonte 30190-002, Minas Gerais, Brazil.

Retinochoroiditis manifests in patients infected with Toxoplasma gondii. Here, we assessed 30 sibships and 89 parent/case trios of presumed ocular toxoplasmosis (POT) to evaluate associations with polymorphisms in the NOD2 gene. Three tag-SNPs within the NOD2 gene were genotyped. The Family Based Association Test (FBAT) showed that the tag-SNP rs3135499 is associated with retinochoroiditis (p=0.039). We then characterized the cellular immune response of 59 cases of POT and 4 of active ocular toxoplasmosis (AOT). We found no differences in IFNγ and IL-2 produced by Th1 lymphocytes when comparing patients with AOT or POT to asymptomatic individuals. Unexpectedly, we found an increased IL-17A production in patients with POT or OAT. In both, patients with POT or AOT, the main cellular source of IL-17A was CD4(+)CD45RO(+)T-bet(-)IFNγ(-) Th17 lymphocytes. Altogether, our results suggest that NOD2 influences the production of IL-17A by CD4(+) T lymphocytes and might contribute to the development of ocular toxoplasmosis.

PMID: 23100559 [PubMed - as supplied by publisher]