Análise do perfil imunológico em recém nascidos com toxoplasmose congênita apresentando diferentes formas clínicas da doença ocular

Abstract

The development of an appropriate immune response is critical for control of T. gondii, but also to reduce the sequelae of congenital infection. Ocular toxoplasmosis is the major clinical manifestation of toxoplasmosis, and understanding of the pathogenic mechanisms involved is crucial for a more appropriate therapeutic approach. In this work we collected the blood of newborns with congenital toxoplasmosis presenting different clinical forms of ocular disease to assess possible changes in immune profile by immunophenotyping of circulating mononuclear cells and analysis of intracytoplasmic cytokines after in vitro stimulation. Our results showed an increase of lymphocytes and monocytes in infected infants. In more detailed analysis, there was an increase of proinflammatory monocytes, indicating that the persistence of the proinflammatory response may be associated with the development of pathology. NK and NK T cells which are important components in the immune response against the parasite were also expanded in infants infected with T. gondii. Analysis of the adaptive immune response showed that CD4+ T cells are apparently associated with the phenotype of active lesion. Additionally, our results demonstrate that CD8+ T cells may be an important biomarker of morbidity in infants infected with T. gondii. Together, results of the phenotypic profile of circulating mononuclear cells in infants with congenital toxoplasmosis suggest maturation of the immune response. Finally we analyzed possible changes in cytokine production by circulating mononuclear cells of infants with congenital toxoplasmosis. In innate immune response we found a mixed profile with a predominance of regulatory cytokines in neutrophils, pro-inflammatory profile modulated by IL-10 in monocytes, and pro-inflammatory profile in NK cells of infants with congenital toxoplasmosis. Analysis of cytokine production by cells of the adaptive immune system shows a pro-inflammatory profile in CD4+ and CD8+ T cells, and regulatory profile in B cells. Analysis of cytokine production in subgroups of TOXO showed increased IL-1Ò and TNF-Ñ levels in cells of infants without active lesions (NRL and CRL) whereas IL-6 and IL-17 cytokines are expanded only in cells of infants with active retinochoroidal lesions (ARL). The major pro-inflammatory cytokines in the control of toxoplasmosis, IL-12 and IFN-× were elevated in all groups of cells from children with congenital infection. The present study is an excellent opportunity to understand key aspects of the immune response during human congenital infection and highlighted possible biomarkers associated with retinochoroidal lesions.