da Matta Vania Lucia R, Gonçalves André N, Gomes Cláudia Maria C, Chouman Islam H, Ferreira Frederico M, Campos Marliane B, Lima Luciana V, Vasconcelos Dos Santos Thiago, Ramos Patrícia Karla, Furtado Rodrigo R, Laurenti Marcia D, Corbett Carlos Eduardo P, Nakaya Helder I, Silveira Fernando T
Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil.
Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil.
Microorganisms. 2023 Mar 3;11(3):653. doi: 10.3390/microorganisms11030653.
Individuals infected with () may present different asymptomatic and symptomatic stages of infection, which vary in the clinical-immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical-immunological (symptomatic and asymptomatic) profiles of human () -infection in the Brazilian Amazon.
感染（）的个体可能呈现出不同的无症状和有症状感染阶段，其临床免疫特征各不相同，可分为无症状感染（AI）、亚临床抗性感染（SRI）、不确定初始感染（III）、亚临床少症状感染（SOI）和有症状感染（SI）（=美洲内脏利什曼病，AVL）。然而，对于具有每种特征的个体之间的分子差异知之甚少。在这里，我们对来自帕拉州（巴西亚马逊地区）的56名感染个体进行了全血转录组分析，涵盖了所有五种特征。然后，我们通过将他们的转录组与来自同一地区的11名健康个体的转录组进行比较，确定了每种特征的基因特征。与无症状的III、AI和SRI特征个体相比，具有SI（=AVL）和SOI特征的有症状个体表现出更高的转录组扰动，这表明疾病严重程度可能与更大的转录组变化相关。尽管许多基因的表达在每种特征中都发生了改变，但很少有基因在这些特征之间共享。这表明每种特征都有独特的基因特征。先天性免疫系统途径仅在无症状的AI和SRI特征中强烈激活，表明感染得到控制。相反，MHC II类抗原呈递和B细胞中NF-κB激活等途径似乎在有症状的SI（=AVL）和SOI特征中被特异性诱导。此外，在那些有症状的特征中，细胞对饥饿的反应被下调。总体而言，这项研究揭示了与巴西亚马逊地区人类（）感染的临床免疫（有症状和无症状）特征相关的五种不同转录模式。
