Department of Master in Environmental Sciences and Health, School of Medical, Pharmaceutical and Biomedical Sciences, Pontifical Catholic University of Goiás, Goiânia, Brazil.
Department of Microbiology, Immunology, Parasitology and Pathology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Brazil.
Front Immunol. 2018 May 3;9:821. doi: 10.3389/fimmu.2018.00821. eCollection 2018.
An early immune response to Zika virus (ZIKV) infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection. These profiles were then associated with symptoms, revealing important aspects of the immunopathophysiology of ZIKV infection. The levels of some cytokines/chemokines were significantly higher in acute ZIKV-infected individuals compared to healthy donors, including interferon (IFN) gamma-induced protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), IFN-γ, interleukin (IL)-9, IL-7, IL-5, and IL-1ra, including some with predominantly immunoregulatory activity. Of note, we found that higher levels of IP-10 and IL-5 in ZIKV-infected individuals were strongly associated with exanthema and headache, respectively. Also, higher levels of IL-1ra were associated with subjects with arthralgia, whereas those with fever showed lower levels of granulocyte-colony stimulating factor (G-CSF). No correlation was observed between the number of symptoms and ZIKV viral load. Interestingly, only IP-10 showed significantly decreased levels in the recovery phase. In conclusion, our results indicate that acute ZIKV infection in a larger cohort resident to an endemic area displays a modest systemic immune activation profile, involving both proinflammatory and immunoregulatory cytokines and chemokines that could participate of virus control. In addition, we showed that differential cytokine/chemokine levels are related to specific clinical symptoms, suggesting their participation in underlying mechanisms.
寨卡病毒（ZIKV）感染的早期免疫反应可能决定其临床表现和结局，包括神经影响。然而，低水平和短暂的病毒血症限制了急性 ZIKV 感染的及时诊断。我们研究了来自流行地区的 36 名个体的血浆细胞因子、趋化因子和生长因子谱，这些个体在感染早期表现出不同的症状，如皮疹、头痛、肌痛、关节痛、发热、充血、肿胀、瘙痒和恶心。然后将这些谱与症状相关联，揭示了 ZIKV 感染免疫病理生理学的重要方面。与健康供体相比，急性 ZIKV 感染个体的一些细胞因子/趋化因子水平显着升高，包括干扰素（IFN）γ诱导蛋白 10（IP-10）、调节激活正常 T 细胞表达和分泌（RANTES）、IFN-γ、白细胞介素（IL）-9、IL-7、IL-5 和 IL-1ra，其中一些具有主要的免疫调节活性。值得注意的是，我们发现 ZIKV 感染个体中 IP-10 和 IL-5 的水平升高与皮疹和头痛分别强烈相关。此外，IL-1ra 水平升高与关节痛患者相关，而发热患者的粒细胞集落刺激因子（G-CSF）水平较低。症状数量与 ZIKV 病毒载量之间没有相关性。有趣的是，只有 IP-10 在恢复期显示出显着降低的水平。总之，我们的结果表明，流行地区的较大队列中的急性 ZIKV 感染显示出适度的全身性免疫激活谱，涉及促炎和免疫调节细胞因子和趋化因子，它们可能参与病毒控制。此外，我们表明，差异细胞因子/趋化因子水平与特定的临床症状相关，表明它们参与潜在机制。
