8 research outputs found
Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections
Toxoplasmosis and ascaridiasis evoke polar Th-1 and Th-2 host immune
responses, respectively. A study to investigate the specific cytokine
profile production by in vitro cultures of peripheral blood mononuclear
cells from individuals living under precarious sanitary conditions in a
highly endemic area for the parasites Toxoplasma gondii and Ascaris
lumbricoides was conducted. High levels of both IFN-γ (Th-1) and
IL-13 (Th-2) were observed in groups of co-infected individuals
presenting toxoplasmic ocular lesions. Significantly lower IL-10 and
TGF-β levels were produced by co-infected individuals in
comparison with groups of individuals not infected with A. lumbricoides
and either positive or negative for T. gondii living under good
sanitary conditions (control groups). The possible influence of
co-parasitism on the clinical presentation of ocular toxoplasmosis is
discussed
Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)
Toxoplasma gondii infection is an important mediator of ocular
disease in Brazil more frequently than reported from elsewhere.
Infection and pathology are characterized by a strong proinflammatory
response which in mice is triggered by interaction of the parasite with
the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify
the role of TLRs in humans is to determine whether polymorphisms at
these loci influence susceptibility to T. gondii mediated pathologies.
Here we report on a small family-based study (60 families; 68 affected
offspring) undertaken in Brazil which was powered for large effect
sizes using single nucleotide polymorphisms with minor alleles
frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these
criteria, we found an association Family Based Association Tests
[(FBAT) Z score = 4.232; p = 1.5 x 10-5; pcorrected = 1.2 x 10-4]
between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence
interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic
retinochoroiditis in Brazil. This supports the hypothesis that direct
interaction between T. gondii and TLR9 may trigger proinflammatory
responses that lead to severe pathologies such as the ocular disease
that is associated with this infection in Brazil
Evidence for associations between the purinergic receptor P2X7 (P2RX7) and toxoplasmosis
Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X 7, encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X7 has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores ± 2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004<P<0.009) when hydrocephalus was removed from the analysis. Association with toxoplasmic retinochoroiditis was replicated (FBAT Z-scores ± 3.089; P=0.002) in a small family-based study (60 families; 68 affected offspring) of acquired infection in Brazil, where the ancestral T(+) allele (f=0.296) at SNP rs1718119 was strongly protective (OR=0.27; 95% CI: 0.09-0.80)