Machado Anderson Silva, Carneiro Ana Carolina Aguiar Vasconcelos, Béla Samantha Ribeiro, Andrade Gláucia Manzan Queiroz, Vasconcelos-Santos Daniel Vitor, Januário José Nélio, Coelho-dos-Reis Jordana G, Ferro Eloisa Amália Vieira, Teixeira-Carvalho Andréa, Vitor Ricardo Wagner Almeida, Martins-Filho Olindo Assis
Departamento de Parasitologia, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Avenida Augusto de Lima, 1715 Barro Preto, 30190-002 Belo Horizonte, MG, Brazil.
Mediators Inflamm. 2014;2014:910621. doi: 10.1155/2014/910621. Epub 2014 Sep 18.
Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14(+)CD16(+)HLA-DR(high) monocytes and CD56(dim) cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ (+) and CD8(+) T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8(+) T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.
弓形虫是人类后部视网膜脉络膜炎的主要感染病因,而后部视网膜脉络膜炎是先天性弓形虫病最常见的临床表现。这项研究是在新生儿筛查后进行的,旨在通过流式细胞术确定与该疾病免疫病理特征相关的免疫生物标志物。该研究纳入了无新生儿视网膜病变(NRL)且患有视网膜脉络膜病变(ARL、ACRL和CRL)的感染婴儿以及未感染个体(NI)。我们的数据表明,白细胞增多,伴有单核细胞和淋巴细胞增加,是ARL的一个相关血液生物标志物。免疫表型分析还显示,ARL中CD14(+)CD16(+)HLA-DR(高)单核细胞和CD56(低)细胞毒性NK细胞扩增。此外,TCRγ δ(+)和CD8(+) T细胞计数增加显然是发病的良好生物标志物。生物标志物网络分析表明,复杂的网络突出了NRL中单核细胞与NK细胞和B细胞的负相关。在ARL中观察到涉及B细胞的连接明显缺乏,以及NK细胞连接从B细胞向T细胞的相关转变,这很突出。在CRL中观察到一个紧密连接的生物标志物网络,NK细胞和CD8(+) T细胞与广泛的细胞亚群有相关连接。我们的发现为先天性弓形虫病先天性和适应性免疫反应的现有知识增添了新元素。