Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-inflammatory Response.
Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-inflammatory Response.
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DOI：
10.3389/fmicb.2020.559255
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发表时间：
2020
影响因子：
5.2
通讯作者：
Kusi KA
中科院分区：
文献类型：
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作者：
Frimpong A;Amponsah J;Adjokatseh AS;Agyemang D;Bentum-Ennin L;Ofori EA;Kyei-Baafour E;Akyea-Mensah K;Adu B;Mensah GI;Amoah LE;Kusi KA
促炎细胞因子和抗炎细胞因子是免疫的重要介质，与疟疾疾病的结果相关。然而，它们在建立无症状感染中的作用（可能先于临床症状的发展）并不清楚。我们确定了促炎细胞因子和抗炎细胞因子以及其他免疫效应分子与无症状疟疾发展的关系。我们使用Luminex测量并比较了无症状疟疾感染（显微镜或亚显微镜）儿童和未感染对照组的促炎介质（包括肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素（IL）-6、IL-12 p70、IL-17 A和颗粒酶B）、抗炎细胞因子IL-4和调节细胞因子IL-10）的血浆水平。我们发现，与未感染的对照组相比，显微镜下无症状疟疾患者的TNF-α和IL-6水平显著升高。与未感染的对照组相比，患有显微镜或亚显微镜下无症状疟疾的儿童表现出更高水平的IFN-γ、IL-17 A和IL-4。大多数促炎和抗炎细胞因子的水平在显微镜和亚显微镜感染的儿童之间是相当的。IFN-γ/IL-10、TNF-α/IL-10、IL-6/IL-10以及IFN-γ/IL-4和IL-6/IL-4的比值在组间无显著差异。此外，使用主成分分析，测量的细胞因子不能区分三个研究人群。这可能意味着无论是显微镜下还是亚显微镜下无症状感染都不会向促炎或抗炎反应极化。数据显示，相对于未感染者，无症状疟疾感染导致促炎细胞因子和抗炎细胞因子的血浆水平增加。然而，促炎细胞因子和抗炎细胞因子之间的平衡在很大程度上得以维持，这可能部分解释了临床症状的缺乏。这与普遍接受的观察结果一致，即临床症状是由于涉及有利于促炎介质的炎性介质平衡失调的免疫病理学而发展的。
Pro- and anti-inflammatory cytokines are important mediators of immunity and are associated with malaria disease outcomes. However, their role in the establishment of asymptomatic infections, which may precede the development of clinical symptoms, is not as well-understood. We determined the association of pro and anti-inflammatory cytokines and other immune effector molecules with the development of asymptomatic malaria. We measured and compared the plasma levels of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-6, IL-12p70, IL-17A, and granzyme B, the anti-inflammatory cytokine IL-4 and the regulatory cytokine IL-10 from children with asymptomatic malaria infections (either microscopic or submicroscopic) and uninfected controls using Luminex. We show that individuals with microscopic asymptomatic malaria had significantly increased levels of TNF-α and IL-6 compared to uninfected controls. Children with either microscopic or submicroscopic asymptomatic malaria exhibited higher levels of IFN-γ, IL-17A, and IL-4 compared to uninfected controls. The levels of most of the pro and anti-inflammatory cytokines were comparable between children with microscopic and submicroscopic infections. The ratio of IFN-γ/IL-10, TNF-α/IL-10, IL-6/IL-10 as well as IFN-γ/IL-4 and IL-6/IL-4 did not differ significantly between the groups. Additionally, using a principal component analysis, the cytokines measured could not distinguish amongst the three study populations. This may imply that neither microscopic nor submicroscopic asymptomatic infections were polarized toward a pro-inflammatory or anti-inflammatory response. The data show that asymptomatic malaria infections result in increased plasma levels of both pro and anti-inflammatory cytokines relative to uninfected persons. The balance between pro- and anti-inflammatory cytokines are, however, largely maintained and this may in part, explain the lack of clinical symptoms. This is consistent with the generally accepted observation that clinical symptoms develop as a result of immunopathology involving dysregulation of inflammatory mediator balance in favor of pro-inflammatory mediators.
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