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Molecular markers of susceptibility to ocular toxoplasmosis, host and guest behaving badly

Authors Vallochi AL, Goldberg AC, Falcai A, Ramasawmy R, Kalil J, Silveira C, Belfort Jr R, Rizzo LV

Published 5 December 2008 Volume 2008:2(4) Pages 837—848


Adriana Lima Vallochi1, Anna Carla Goldberg2, Angela Falcai3, Rajendranath Ramasawmy4, Jorge Kalil4, Cláudio Silveira5, Rubens Belfort Jr5, Luiz Vicente Rizzo3

1Oswaldo Cruz Institution (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, Brazil; 2NUCEL – Cellular and Molecular Therapy Center, University of São Paulo, São Paulo, SP, Brazil; 3Department of Immunology, Biomedical Science Institute, University of São Paulo, São Paulo, SP, Brazil; 4Laboratory of Immunology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil; 5Department of Ophthalmology, Federal University of São Paulo, São Paulo, SP, Brazil

Abstract: Infection with Toxoplasma gondii results in retinochoroiditis in 6% to 20% of immunocompetent individuals. The outcome of infection is the result of a set of interactions involving host genetic background, environmental, and social factors, and the genetic background of the parasite, all of which can be further modified by additional infections or even reinfection. Genes that encode several components of the immune system exhibit polymorphisms in their regulatory and coding regions that affect level and type of expression in response to stimuli, directing the immune response into different pathways. These variant alleles have been associated with susceptibility to immune-mediated diseases and with severity of pathology. We have investigated polymorphisms in several of these genes, identified as candidates for progression to retinochoroiditis caused by toxoplasmosis, namely chemokine (C-C motif) receptor 5 (CCR5), toll-like receptor-2 (TLR2), and TLR4. Furthermore, because interleukin-12 (IL-12) has been shown to be fundamental both in mice and in man to control a protective response against T. gondii, molecules that have a key function in IL-12 production will be emphasized in this review, in addition to discussing the importance of the genetic background of the parasite in the establishment of ocular disease.

Keywords: ocular toxoplasmosis, IL-12, TLR, CCR5, immunity

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