Arce Miranda Julio E, Baronetti José L, Sotomayor Claudia E, Paraje M Gabriela
IMBIV-National Scientific and Technical Research Council (CONICET) and Department of Physiology, Faculty of Exact, Physical and Natural Sciences, National University of Córdoba, Córdoba, Argentina.
CIBICI-National Scientific and Technical Research Council (CONICET) and Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.
Med Mycol. 2019 Jan 1;57(1):101-113. doi: 10.1093/mmy/myx143.
Candida albicans is an important source of device-associated infection because of its capacity for biofilm formation. This yeast has the ability to form biofilms which favors the persistence of the infection. Furthermore, the innate immune response has a critical role in the control of these infections and macrophages (Mø) are vital to this process. An important fungicidal mechanism employed by Mø involves the generation of toxic reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI). The interaction between biofilms and these immune cells, and the contribution of oxidative and nitrosative stress, that is determinant to the course of the infection, remains elusive. The aim of this study was to investigate this interaction. To this purpose, two models of Mø-biofilms contact, early (model 1) and mature (model 2) biofilms, were used; and the production of ROS, RNI and the oxidative stress response (OSR) were evaluated. We found that the presence of Mø decreased the biofilm formation at an early stage and increased the production of ROS and RNI, with activation of ORS (enzymatic and nonenzymatic). On the other hand, the interaction between mature biofilms and Mø resulted in an increasing biofilm formation, with low levels of RNI and ROS production and decrease of OSR. Dynamic interactions between Mø and fungal biofilms were also clearly evident from images obtained by confocal scanning laser microscopy. The prooxidant-antioxidant balance was different depending of C. albicans biofilms stages and likely acts as a signal over their formation in presence of Mø. These results may contribute to a better understanding of the immune-pathogenesis of C. albicans biofilm infections.
白色念珠菌因其形成生物膜的能力而成为与器械相关感染的重要来源。这种酵母菌能够形成生物膜，这有利于感染的持续存在。此外，固有免疫反应在控制这些感染中起关键作用，巨噬细胞（Mø）对这一过程至关重要。Mø采用的一种重要杀菌机制涉及产生活性氧（ROS）和活性氮中间体（RNI）。生物膜与这些免疫细胞之间的相互作用，以及氧化应激和亚硝化应激对感染进程的决定性作用，仍不清楚。本研究的目的是调查这种相互作用。为此，使用了两种Mø与生物膜接触的模型，早期（模型1）和成熟（模型2）生物膜；并评估了ROS、RNI的产生以及氧化应激反应（OSR）。我们发现，Mø的存在在早期减少了生物膜的形成，并增加了ROS和RNI的产生，同时激活了ORS（酶促和非酶促）。另一方面，成熟生物膜与Mø之间的相互作用导致生物膜形成增加，RNI和ROS产生水平较低，OSR降低。通过共聚焦扫描激光显微镜获得的图像也清楚地显示了Mø与真菌生物膜之间的动态相互作用。根据白色念珠菌生物膜的阶段，促氧化剂-抗氧化剂平衡不同，并且在Mø存在的情况下可能作为其形成的信号。这些结果可能有助于更好地理解白色念珠菌生物膜感染的免疫发病机制。
