Mycobacterial Diseases
Open Access

Balancing Immunity and Inflammation in Pulmonary Tuberculosis

Honghuan Zhu^{* *}Correspondence: Honghuan Zhu, Department of Pharmaceutics, Fudan University, Shanghai, China, Email:

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Description

The characteristic of Tuberculosis (TB) is the involvement of the lungs, leading to inflammation, granuloma formation, and tissue destruction. Inflammation plays a dual role in TB: While it helps to contain the infection, it also contributes to tissue damage and disease progression. Understanding how inflammation leads to tissue damage in pulmonary TB is essential for developing therapeutic strategies to control the disease while minimizing lung destruction. When Mycobacterium tuberculosis (M. tb) enters the lungs, it is phagocytosed by alveolar macrophages, which act as the first line of defense. However, M. tb has evolved mechanisms to survive within macrophages, evading the immune system. As the immune response is activated, additional immune cells, including neutrophils, monocytes, and lymphocytes, are recruited to the site of infection. This leads to the formation of granulomas-organized clusters of immune cells that attempt to contain the infection. The primary role of the immune system in TB is to contain M. tb within these granulomas and prevent its spread.

Role of cytokines and chemokines in inflammation

Cytokines and chemokines are key mediators of the immune response in TB. Pro-inflammatory cytokines such as Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1β (IL-1β), and Interferon-Gamma (IFN-γ) are essential for activating immune cells and controlling bacterial growth. TNF-α, in particular, is important for the formation and maintenance of granulomas. However, an excessive or dysregulated production of proinflammatory cytokines can exacerbate lung damage. TNF-α, while protective, is also a mediator of inflammation-induced necrosis. High levels of TNF-α can lead to the destruction of lung parenchyma, contributing to the characteristic cavitation seen in advanced TB. Similarly, IFN-γ enhances the bactericidal activity of macrophages but can also drive excessive inflammation, resulting in tissue destruction. Chemokines, such as CXCL10 and CCL2, play a role in recruiting immune cells to the site of infection. While necessary for controlling the infection, the continuous influx of neutrophils and macrophages can result in the release of Reactive Oxygen Species (ROS), proteases, and other cytotoxic molecules, which further contribute to tissue damage.

Granuloma formation and tissue damage

Granulomas are the central feature of the immune response in TB, functioning as both a containment structure and a site of tissue damage. In the early stages of infection, granulomas can control bacterial replication. However, as the disease progresses, granulomas can break down, leading to the release of bacteria and inflammatory mediators into the surrounding lung tissue. The breakdown of granulomas is often associated with necrosis, particularly caseous necrosis, where the tissue becomes soft and cheese-like. This necrosis is caused by a combination of factors, including the immune response, the action of cytotoxic T cells, and the release of proteolytic enzymes by immune cells. As granulomas collapse, they form cavities in the lungs, which are characteristic of advanced pulmonary TB. These cavities are sites of high bacterial load and contribute to both disease transmission and severe lung damage. Neutrophils play an important role in the immune response to TB but are also key contributors to tissue damage. While they can kill M. tb, they also release enzymes such as Matrix Metalloproteinases (MMPs) and elastases, which degrade the extracellular matrix and damage lung tissue. Neutrophils also produce ROS, which can exacerbate inflammation and tissue injury. In advanced TB, neutrophil-dominated inflammation is associated with the formation of cavities and extensive lung destruction.

Fibrosis and long term consequences

In addition to acute tissue damage caused by inflammation, chronic inflammation can lead to fibrosis, or scarring of the lung tissue. Fibrosis occurs as the body attempts to repair damaged tissue, but it can lead to reduced lung function and long-term respiratory problems. In some cases, the fibrosis can be so extensive that it leads to restrictive lung disease, limiting the patient’s ability to breathe. Given the role of inflammation in both controlling M. tb and causing tissue damage, there isgrowing interest in developing therapies that modulate the immune response. Anti-inflammatory treatments, such as corticosteroids, are already used in certain cases of TB, such as TB meningitis, to reduce inflammation. However, more targeted approaches are needed to balance the immune response without compromising the body's ability to fight the infection. Therapies that specifically target inflammatory mediators, such as TNF-α inhibitors, may help reduce tissue damage, but they carry the risk of increasing susceptibility to infection.

Conclusion

Inflammation-mediated tissue damage is a major factor in the pathology of pulmonary TB. While the immune response is essential for controlling M. tb, excessive or prolonged inflammation can lead to significant lung damage, contributing to morbidity and mortality in TB patients. Future therapies that can modulate inflammation without impairing the immune response may hold the key to reducing the tissue damage associated with TB while maintaining control over the infection. However, the immune response, particularly the inflammatory component, also plays a significant role in tissue damage. Chronic inflammation and the over activation of immune cells can lead to collateral damage to the surrounding lung tissue.