Carneiro Ana Carolina Aguiar Vasconcelos, Machado Anderson Silva, Béla Samantha Ribeiro, Costa Julia Gatti Ladeia, Andrade Gláucia Manzan Queiroz, Vasconcelos-Santos Daniel Vitor, Januário José Nélio, Coelho-Dos-Reis Jordana Grazziela, Ferro Eloisa Amália Vieira, Teixeira-Carvalho Andréa, Vitor Ricardo Wagner Almeida, Martins-Filho Olindo Assis
Departamento de Parasitologia.
Grupo Integrado de Pesquisas em Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz.
J Infect Dis. 2016 Jun 15;213(12):1962-70. doi: 10.1093/infdis/jiw041. Epub 2016 Mar 5.
Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants.
Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection.
Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions.
These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management.
眼部弓形虫病在巴西是一种高发的突出且严重的疾病。本研究为人类婴儿先天性弓形虫病背景下与视网膜脉络膜炎相关的免疫事件提供了新的见解。
对先天性弓形虫感染婴儿进行体外短期抗原激发后,对白细胞亚群中的胞质内细胞因子进行流式细胞术检测。
我们的数据表明,虽然来自弓形虫感染婴儿的中性粒细胞和单核细胞表现出促炎和调节性细胞因子谱的组合,但自然杀伤细胞在体外弓形虫刺激后主要表现出促炎谱。在患有活动性视网膜脉络膜病变的患者中,以产生干扰素γ(IFN-γ)和白细胞介素17为特征的CD4(+)和CD8(+) T细胞的促炎反应,揭示了在早期和晚期免疫事件中存在IFN-γ和肿瘤坏死因子α。这种特定的促炎模式与早期事件和活动性视网膜脉络膜病变相关,而在患有瘢痕性眼部病变的儿童中观察到由单核细胞衍生的白细胞介素10介导的强大模式。
这些发现支持在先天性弓形虫病婴儿视网膜脉络膜病变形成过程中存在与初始、急性期和瘢痕期相伴的渐进性免疫环境,这可能与制定阶段特异性临床管理相关。