title: Association of a NOD2 gene polymorphism and T-helper 17 cells with presumed ocular toxoplasmosis.
abstract: 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 haplotype-tagging single-nucleotide polymorphisms (tag-SNPs) within the NOD2 gene were genotyped. The family-based association test showed that the tag-SNP rs3135499 is associated with retinochoroiditis (P = .039). We then characterized the cellular immune response of 59 cases of POT and 4 cases of active ocular toxoplasmosis (AOT). We found no differences in levels of interferon γ (IFN-γ) and interleukin 2 produced by T-helper 1 cells when comparing patients with AOT or POT to asymptomatic individuals. Unexpectedly, we found an increased interleukin 17A (IL-17A) production in patients with POT or OAT. In patients with POT or AOT, the main cellular source of IL-17A was CD4(+)CD45RO(+)T-bet(-)IFN-γ(-) T-helper 17 cells. 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.
authors.affiliation: Centro de Pesquisas René Rachou,  CPqRR-Fundação Oswaldo Cruz, FIOCRUZ, Belo Horizonte, Brazil.
authors.forename: Míriam S
authors.initials: MS
authors.lastname: Dutra
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Béla
authors.forename: Alba L
authors.initials: AL
authors.lastname: Peixoto-Rangel
authors.forename: Michaela
authors.initials: M
authors.lastname: Fakiola
authors.forename: Ariane G
authors.initials: AG
authors.lastname: Cruz
authors.forename: Andrea
authors.initials: A
authors.lastname: Gazzinelli
authors.forename: Humberto F
authors.initials: HF
authors.lastname: Quites
authors.forename: Lilian M G
authors.initials: LM
authors.lastname: Bahia-Oliveira
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Peixe
authors.forename: Wesley R
authors.initials: WR
authors.lastname: Campos
authors.forename: Anna C
authors.initials: AC
authors.lastname: Higino-Rocha
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Miller
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
authors.forename: Lis R
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D015331:Cohort Studies; D016207:Cytokines / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014126:Toxoplasmosis, Ocular / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D020381:Interleukin-17; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein