Date of Award

2025-05-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Jianjun Sun

Abstract

Tuberculosis (TB) remains a leading cause of mortality, particularly in underdeveloped regions. Mycobacterium tuberculosis (Mtb) is regarded as one of the most successful pathogens due to its ability to evade host immunity and persist within granulomas. Macrophages are the first-line host defenders that engulf Mtb into phagosomes, which initiates lysosomal activity for degradation. However, the virulence factor of Mtb is able to inhibit phagolysosome fusion. The host immune system forms granulomas to contain the mycobacterium at the site of inflammation. This, in turn, causes a necrotic state and causes tissue damage from the prolonged inflammation. Studies suggest that the host's inflammatory response contributes more to tissue damage than the pathogen itself. This gives a different point of view in infectious disease treatment, where therapeutic strategies should balance tissue repair and host-immune-induced damage. To address this, we have developed a mathematical Host-Pathogen Interaction (HPI) model that highlights the importance of the host's ability to repair (termed self-healing power) in infection recovery. This model suggests that host survival relies on an optimal balance between immune-mediated pathogen control and healing-mediated tissue repair. However, current literature often conflates the host's healing mechanisms with immune function, and there is no quantitative framework to determine how much immune activation is detrimental to tissue repair. To clarify this distinction, we use alveolar macrophages as a model system due to their diverse roles in TB pathogenesis, including pro-inflammatory responses, anti-inflammatory activities, and tissue repair functions. This review aims to characterize macrophage heterogeneity, polarization, and their roles in both immune defense and tissue repair, leading to the definition of the host's healing function as a distinct entity from immune function within the framework of the HPI model. By distinguishing between tissue repair and immune defense, this work provides a theoretical foundation for developing therapeutic strategies that enhance self-healing while maintaining immune balance, ultimately contributing to improved TB treatment approaches.

Language

en

Provenance

Received from ProQuest

File Size

69 p.

File Format

application/pdf

Rights Holder

Blessing Savusa

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Biology Commons

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