Laboratory of Host-Parasite Interaction and Epidemiology, Gonçalo Moniz Institute, Fiocruz-Bahia, Salvador, Brazil.
National Institute of Tropical Disease, Brasilia, Brazil.
Front Cell Infect Microbiol. 2018 Sep 19;8:326. doi: 10.3389/fcimb.2018.00326. eCollection 2018.
Leishmaniasis is a vector-borne, neglected tropical disease with a worldwide distribution that can present in a variety of clinical forms, depending on the parasite species and host genetic background. The pathogenesis of this disease remains far from being elucidated because the involvement of a complex immune response orchestrated by host cells significantly affects the clinical outcome. Among these cells, macrophages are the main host cells, produce cytokines and chemokines, thereby triggering events that contribute to the mediation of the host immune response and, subsequently, to the establishment of infection or, alternatively, disease control. There has been relatively limited commercial interest in developing new pharmaceutical compounds to treat leishmaniasis. Moreover, advances in the understanding of the underlying biology of spp. have not translated into the development of effective new chemotherapeutic compounds. As a result, biomarkers as surrogate disease endpoints present several potential advantages to be used in the identification of targets capable of facilitating therapeutic interventions considered to ameliorate disease outcome. More recently, large-scale genomic and proteomic analyses have allowed the identification and characterization of the pathways involved in the infection process in both parasites and the host, and these analyses have been shown to be more effective than studying individual molecules to elucidate disease pathogenesis. RNA-seq and proteomics are large-scale approaches that characterize genes or proteins in a given cell line, tissue, or organism to provide a global and more integrated view of the myriad biological processes that occur within a cell than focusing on an individual gene or protein. Bioinformatics provides us with the means to computationally analyze and integrate the large volumes of data generated by high-throughput sequencing approaches. The integration of genomic expression and proteomic data offers a rich multi-dimensional analysis, despite the inherent technical and statistical challenges. We propose that these types of global analyses facilitate the identification, among a large number of genes and proteins, those that hold potential as biomarkers. The present review focuses on large-scale studies that have identified and evaluated relevant biomarkers in macrophages in response to infection.
利什曼病是一种具有全球分布的、被忽视的热带病，由媒介传播，其临床表现多种多样，取决于寄生虫种类和宿主遗传背景。该疾病的发病机制仍远未阐明，因为宿主细胞协调的复杂免疫反应显著影响临床结果。在这些细胞中，巨噬细胞是主要的宿主细胞，它们产生细胞因子和趋化因子，从而引发有助于介导宿主免疫反应的事件，并随后导致感染的建立或疾病的控制。开发治疗利什曼病的新药物化合物的商业兴趣相对有限。此外，对 spp. 潜在生物学的理解进展并没有转化为有效新化学治疗化合物的开发。因此，作为替代疾病终点的生物标志物具有一些潜在的优势，可用于鉴定能够促进被认为改善疾病结果的治疗干预的目标。最近，大规模基因组和蛋白质组学分析允许鉴定和描述寄生虫和宿主感染过程中涉及的途径，并且这些分析已被证明比研究单个分子更有效地阐明疾病发病机制。RNA-seq 和蛋白质组学是大规模方法，用于表征给定细胞系、组织或生物体中的基因或蛋白质，以提供比单个基因或蛋白质更全面和更综合的细胞内众多生物过程的视图。生物信息学为我们提供了计算分析和整合高通量测序方法产生的大量数据的手段。基因组表达和蛋白质组学数据的整合提供了丰富的多维分析，尽管存在内在的技术和统计挑战。我们提出，这些类型的全局分析有助于在大量基因和蛋白质中鉴定具有作为生物标志物潜力的基因和蛋白质。本综述重点介绍了已识别和评估巨噬细胞中与 感染反应相关的相关生物标志物的大规模研究。
