ABSTRACT
CC chemokine receptor type 5 (CCR5) is a chemokine receptor that influences the immune response to infectious and parasitic diseases. This study aimed to determine whether the CCR5Δ32 and CCR5 59029 A/G polymorphisms are associated with the development of ocular toxoplasmosis in humans. Patients with positive serology for Toxoplasma gondii were analyzed and grouped as 'with ocular toxoplasmosis' (G1: n=160) or 'without ocular toxoplasmosis' (G2: n=160). A control group (G3) consisted of 160 individuals with negative serology. The characterization of the CCR5Δ32 and CCR5 59029 A/G polymorphisms was by PCR and by PCR-RFLP, respectively. The difference between the groups with respect to the mean age (G1: mean age: 47.3, SD±19.3, median: 46 [range: 18-95]; G2: mean age: 61.3, SD±13.7, median: 61 [range: 21-87]; G3: mean age: 38.8, SD±17.9, median: 34 [range: 18-80]) was statistically significant (G1 vs.G2: p-value <0.0001; t=7.21; DF=318; G1 vs.G3: p-value <0.0001; t=4.32; DF=318; G2 vs. G3: p-value <0.0001; t=9.62; DF=318). The Nagelkerke r2 value was 0.040. There were statistically significant differences for the CCR5/CCR5 (p-value=0.008; OR=0.261), AA (p-value=0.007; OR=2.974) and AG genotypes (p-value=0.018; OR=2.447) between G1 and G2. Individuals with the CCR5/CCR5 genotype and simultaneously the CCR5-59029 AA or AG genotypes have a greater risk of developing ocular toxoplasmosis (4% greater), which may be associated with a strong and persistent inflammatory response in ocular tissue.
Subject(s)
Genetic Predisposition to Disease , Polymorphism, Genetic , Receptors, CCR5/genetics , Toxoplasmosis, Ocular/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Aging , Case-Control Studies , Female , Genotype , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors , Toxoplasma , Toxoplasmosis, Ocular/parasitology , Young AdultABSTRACT
Chagas disease is an infection caused by the protozoan Trypanosoma cruzi. The clinical manifestations result from the chronic forms of the disease: indeterminate, cardiac, digestive or mixed. The pathogenesis of this disease is related to the genetic variability of both the parasite and the host with polymorphisms of genes involved in immune response possibly being involved in the variable clinical course. Cytokines play a key role in regulating immune response, in particular chemokines exert a crucial role in the control of leukocyte migration during the host's response to infectious processes. Furthermore, inflammatory cytokines and chemokines have been implicated in the generation of inflammatory infiltrates and tissue damage. The involvement of the CC Chemokine Receptor 5 (CCR5) in leukocyte migration to sites of inflammation has been elucidated and this receptor has been investigated in Chagas disease. Here we review the role of CCR5 in T. cruzi infection as well as its importance in the pathogenesis of the Chagas disease.
