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The MPO system participates actively in the formation of an oxidative environment produced by neutrophils and activates the antioxidant mechanism of Naegleria fowleri.
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-06-12 , DOI: 10.1002/jlb.4ma0520-565rr Nadia Flores-Huerta 1 , Judith Pacheco-Yépez 2 , Virginia Sánchez-Monroy 3 , Martha Cecilia Rosales-Hernández 4 , Angélica Silva-Olivares 1 , Jesús Serrano-Luna 5 , Mineko Shibayama 1
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-06-12 , DOI: 10.1002/jlb.4ma0520-565rr Nadia Flores-Huerta 1 , Judith Pacheco-Yépez 2 , Virginia Sánchez-Monroy 3 , Martha Cecilia Rosales-Hernández 4 , Angélica Silva-Olivares 1 , Jesús Serrano-Luna 5 , Mineko Shibayama 1
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Naegleria fowleri produces a fatal disease called primary amebic meningoencephalitis (PAM), which is characterized by an extensive inflammatory reaction in the CNS. It is known that the immune response is orchestrated mainly by neutrophils, which activate several defense mechanisms in the host, including phagocytosis, the release of different enzymes such as myeloperoxidase (MPO), and the production of neutrophil extracellular traps. However, the mechanisms by which amoebas evade the neutrophil response are still unknown. In this study, we analyzed the ability of N. fowleri to respond to the stress exerted by MPO. Interestingly, after the interaction of trophozoites with neutrophils, the amoeba viability was not altered; however, ultrastructural changes were observed. To analyze the influence of MPO against N. fowleri and its participation in free radical production, we evaluated its enzymatic activity, expression, and localization with and without the specific 4‐aminobenzoic acid hydrazide inhibitor. The production of oxidizing molecules is the principal mechanism used by neutrophils to eliminate pathogens. In this context, we demonstrated an increase in the production of NO, superoxide anion, and reactive oxygen species; in addition, the overexpression of several antioxidant enzymes present in the trophozoites was quantified. The findings strongly suggest that N. fowleri possesses antioxidant machinery that is activated in response to an oxidative environment, allowing it to evade the neutrophil‐mediated immune response, which may contribute to the establishment of PAM.
中文翻译：
MPO系统积极参与中性粒细胞产生的氧化环境的形成，并激活家禽（Naegleria fowleri）的抗氧化机制。
禽流感菌可导致致命疾病，称为原发性阿米巴脑膜脑炎（PAM），其特征是中枢神经系统发生广泛的炎症反应。众所周知，免疫反应主要是由嗜中性粒细胞精心策划的，嗜中性粒细胞激活了宿主中的几种防御机制，包括吞噬作用，诸如髓过氧化物酶（MPO）等不同酶的释放以及嗜中性粒细胞胞外陷阱的产生。但是，变形虫逃避中性粒细胞反应的机制仍是未知的。在这项研究中，我们分析了福勒猪笼草的能力应对MPO施加的压力。有趣的是，滋养体与中性粒细胞相互作用后，变形虫的生存能力没有改变。然而，观察到超微结构的变化。为了分析MPO对N. fowleri的影响及其参与自由基产生的过程，我们评估了有无特定4-氨基苯甲酸酰肼抑制剂时其MPO的酶活性，表达和定位。氧化分子的产生是中性粒细胞消除病原体的主要机制。在这种情况下，我们证明了NO，超氧阴离子和活性氧的产生有所增加。此外，对滋养体中存在的几种抗氧化酶的过表达进行了定量。研究结果强烈表明福勒猪笼草具有抗氧化机制，可在氧化环境中被激活，从而逃避中性粒细胞介导的免疫反应，这可能有助于建立PAM。
更新日期：2020-06-12
中文翻译：
MPO系统积极参与中性粒细胞产生的氧化环境的形成，并激活家禽（Naegleria fowleri）的抗氧化机制。
禽流感菌可导致致命疾病，称为原发性阿米巴脑膜脑炎（PAM），其特征是中枢神经系统发生广泛的炎症反应。众所周知，免疫反应主要是由嗜中性粒细胞精心策划的，嗜中性粒细胞激活了宿主中的几种防御机制，包括吞噬作用，诸如髓过氧化物酶（MPO）等不同酶的释放以及嗜中性粒细胞胞外陷阱的产生。但是，变形虫逃避中性粒细胞反应的机制仍是未知的。在这项研究中，我们分析了福勒猪笼草的能力应对MPO施加的压力。有趣的是，滋养体与中性粒细胞相互作用后，变形虫的生存能力没有改变。然而，观察到超微结构的变化。为了分析MPO对N. fowleri的影响及其参与自由基产生的过程，我们评估了有无特定4-氨基苯甲酸酰肼抑制剂时其MPO的酶活性，表达和定位。氧化分子的产生是中性粒细胞消除病原体的主要机制。在这种情况下，我们证明了NO，超氧阴离子和活性氧的产生有所增加。此外，对滋养体中存在的几种抗氧化酶的过表达进行了定量。研究结果强烈表明福勒猪笼草具有抗氧化机制，可在氧化环境中被激活，从而逃避中性粒细胞介导的免疫反应，这可能有助于建立PAM。
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