The Macrophage: A Disputed Fortress in the Battle against Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB), has plagued humans for thousands of years. TB still remains a major public health problem in our era, causing more than 4,400 deaths worldwide every day and killing more people than HIV. After inhaling Mtb-contaminated aerosols, TB primo-infection starts in the terminal lung airways, where Mtb is taken up by alveolar macrophages. Although macrophages are known as professional killers for pathogens, Mtb has adopted remarkable strategies to circumvent host defenses, building suitable conditions to survive and proliferate. Within macrophages, Mtb initially resides inside phagosomes, where its survival mostly depends on its ability to take control of phagosomal processing, through inhibition of phagolysosome biogenesis and acidification processes, and by progressively getting access to the cytosol. Bacterial access to the cytosolic space is determinant for specific immune responses and cell death programs, both required for the replication and the dissemination of Mtb. Comprehension of the molecular events governing Mtb survival within macrophages is fundamental for the improvement of vaccine-based and therapeutic strategies in order to help the host to better defend itself in the battle against the fierce invader Mtb. In this mini-review, we discuss recent research exploring how Mtb conquers and transforms the macrophage into a strategic base for its survival and dissemination as well as the associated defense strategies mounted by host.

Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma

“…iNOS-derived NO plays a key role in host defense against mycobacteria 34 . A variety of M. tuberculosis determinants allow the evasion from macrophage bactericidal mechanisms 35 . Relevant for our data, M. tuberculosis can detect oxidative-nitrosative induced changes in the host environment 36 and respond by producing proteins that limit the toxic effects of these changes, including enzymes that repair NO-damaged bacterial proteins at the proteasome level [37][38][39] .…”

E-cigarettes: Effects in phagocytosis and cytokines response against Mycobacterium tuberculosis

“…Innate immune response is crucial for the outcome of TB infection as well as for the adaptive immune response [44]. Macrophages are a pivotal piece of the innate immunity for TB and its response is affected by cigarette smoke and e-vapor.…”

<p>Silver Nanoparticles for the Therapy of Tuberculosis</p>

“…96 In a dynamic representation of this pathogenicity, the macrophage and neutrophil necrosis represents the starting point for a vicious cycle which continues with the uptake of the Mtb-infected cell debris from the newly recruited monocytes and neutrophils, de novo Mtb replication, sustained infection and finally the induction of cell death. 96,97 The mycobacteria can utilize this growing niche for enhanced replication and survival, contributes to the success of mycobacteria to resist host defense and antibacterial therapy. 95,97 Metallic Nanoparticles as Antiinfective Agents…”