Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Peixoto-Rangel, Alba L.; Miller, E.N.; Castellucci, Léa; Jamieson, Sarra E.; Peixe, Ricardo Guerra; Elias, Liliani de Souza; Correa-Oliveira, Rodrigo; Bahia-Oliveira, Lilian M. G.; Blackwell, Jenefer M.

doi:10.1590/s0074-02762009000800019

Cited by 42 publications

(35 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, we found evidence of the association of two tag-SNPs (i.e., rs1461567 and rs4251513) distributed in the IRAK4 gene with brain and ocular alterations in congenital toxoplasmosis. Taken together, the associations of SNPs in TLR9 with retinochoroiditis (37) and in IRAK4 with congenital toxoplasmosis support the hypothesis that TLRs are critical in mediating resistance to T. gondii infection in humans.…”

Section: Discussionsupporting

confidence: 61%

Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii

et al. 2012

View full text Add to dashboard Cite

e Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a member of the IRAK family and has an important role in inducing the production of inflammatory mediators. This kinase is downstream of MyD88, an adaptor protein essential for Toll-like receptor (TLR) function. We investigated the role of this kinase in IRAK4-deficient mice orally infected with the cystogenic ME49 strain of Toxoplasma gondii. IRAK4 ؊/؊ mice displayed higher morbidity, tissue parasitism, and accelerated mortality than the control mice. The lymphoid follicles and germinal centers from infected IRAK4 ؊/؊ mice were significantly smaller. We consistently found that IRAK4 ؊/؊ mice showed a defect in splenic B cell activation and expansion as well as diminished production of gamma interferon (IFN-␥) by T lymphocytes. The myeloid compartment was also affected. Both the frequency and ability of dendritic cells (DCs) and monocytes/macrophages to produce IL-12 were significantly decreased, and resistance to infection with Toxoplasma was rescued by treating IRAK4 ؊/؊ mice with recombinant IL-12 (rIL-12). Additionally, we report the association of IRAK4 haplotype-tagging single nucleotide polymorphisms (tag-SNPs) with congenital toxoplasmosis in infected individuals (rs1461567 and rs4251513, P < 0.023 and P < 0.045, respectively). Thus, signaling via IRAK4 is essential for the activation of innate immune cells, development of parasite-specific acquired immunity, and host resistance to infection with T. gondii.

show abstract

Section: Discussionsupporting

confidence: 61%

Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Supported by a small family-based study in children with congenital ocular toxoplasmosis, a significant association between gene polymorphisms of TLR (TLR2, TLR5 and TLR9) was reported [42]. …”

Section: Host Genetic Factors: Do They Play a Role In The Susceptibilmentioning

confidence: 99%

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Pleyer

Schlüter

Mänz³

2014

Ophthalmic Res

View full text Add to dashboard Cite

Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome.

show abstract

“…However, we believe that information regarding their size and localization could be useful for future comparative studies in other endemic areas of Brazil and abroad. We present the frequency of localization and sizes of 85 scar lesions from 49 patients, some of which were involved in immunological and immunogenetic studies conducted in Campos [16][17][18]. In Figure 2, a fundoscopy picture from a normal (presenting no retinal damage) individual is shown.…”

Section: The Diversity Of Retinal/retinochoroidal Scar Lesions In T mentioning

confidence: 99%

“…We have conducted genetic association studies of candidate genes which potentially influence the profile of the inflammatory response against T. gondii (17,18,37) in patients with ocular toxoplasmosis by means of single nucleotide polymorphisms (SNPs) analysis. Significant associations between genetic polymorphisms and ocular disease in family-based studies have been found for Toll-like receptor-9, (TLR-9) [17], P2X7 purinoceptor 7 (P2RX7) [18] and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) [37] genes. These studies are currently being expanded to be replicated into population n-based investigational projects.…”

Section: Immunogenetic Studies: Candidate Genes On Ocular Toxoplasmosismentioning

confidence: 99%

“…These studies are currently being expanded to be replicated into population n-based investigational projects. All of these genes are related to innate immunity and have been described in processes of inflammasome assembly, which plays an important role in processing IL-1 beta and other IL-1 beta cytokine family member (IL-18, IL-33) precursors in active cytokines, promoting a pro-inflammatory response [44].The SNPs rs352140 at TLR-9 and rs3135499 at NOD2 were statistically significantly associated with the manifestation of ocular toxoplasmosis [17,37] while the absence of the SNP rs1718119 at P2RX7 was strongly associated with protection to ocular disease manifestation [18] as we shall see in detail.…”

Section: Immunogenetic Studies: Candidate Genes On Ocular Toxoplasmosismentioning

confidence: 99%

See 1 more Smart Citation

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

Bahia-Oliveira¹,

Rangel²,

Boechat³

et al. 2012

Toxoplasmosis - Recent Advances

View full text Add to dashboard Cite

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Abstract: Toxoplasma gondii infection is an important mediator of ocular disease in

Cited by 42 publications

References 24 publications

Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii

Impaired Innate Immunity in Mice Deficient in Interleukin-1 Receptor-Associated Kinase 4 Leads to Defective Type 1 T Cell Responses, B Cell Expansion, and Enhanced Susceptibility to Infection with Toxoplasma gondii

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

Contact Info

Product

Resources

About