Host-Pathogen Interactions Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Center for Interdisciplinary Research in Health, Católica Medical School, Universidade Católica Portuguesa, Estrada Octávio Pato, 2635-631 Rio de Mouro, Portugal.
Biomolecules. 2024 Jul 14;14(7):848. doi: 10.3390/biom14070848.
Tuberculosis and AIDS remain two of the most relevant human infectious diseases. The pathogens that cause them, (Mtb) and HIV, individually elicit an immune response that treads the line between beneficial and detrimental to the host. Co-infection further complexifies this response since the different cytokines acting on one infection might facilitate the dissemination of the other. In these responses, the role of type I interferons is often associated with antiviral mechanisms, while for bacteria such as Mtb, their importance and clinical relevance as a suitable target for manipulation are more controversial. In this article, we review the recent knowledge on how these interferons play distinct roles and sometimes have opposite consequences depending on the stage of the pathogenesis. We highlight the dichotomy between the acute and chronic infections displayed by both infections and how type I interferons contribute to an initial control of each infection individually, while their chronic induction, particularly during HIV infection, might facilitate Mtb primo-infection and progression to disease. We expect that further findings and their systematization will allow the definition of windows of opportunity for interferon manipulation according to the stage of infection, contributing to pathogen clearance and control of immunopathology.
结核病和艾滋病仍然是两种最重要的人类传染病。引起它们的病原体，结核分枝杆菌（Mtb）和 HIV，各自引发的免疫反应在对宿主有益和有害之间徘徊。合并感染进一步使这种反应复杂化，因为作用于一种感染的不同细胞因子可能会促进另一种感染的传播。在这些反应中，I 型干扰素的作用通常与抗病毒机制相关，而对于 Mtb 等细菌，它们作为操纵的合适靶点的重要性和临床相关性更具争议性。在本文中，我们回顾了最近关于这些干扰素如何根据发病机制的不同阶段发挥不同作用，有时产生相反后果的知识。我们强调了这两种感染所表现出的急性和慢性感染之间的二分法，以及 I 型干扰素如何有助于单独控制每种感染，而其慢性诱导，特别是在 HIV 感染期间，可能会促进 Mtb 初次感染和疾病进展。我们预计，进一步的发现及其系统化将允许根据感染阶段定义干扰素操纵的机会窗口，有助于清除病原体和控制免疫病理学。
