Mycobacterial Diseases
Open Access

Exploring Tuberculosis through Host-Pathogen Interactions

Nicolas Kelydson^{* *}Correspondence: Nicolas Kelydson, Division of Immunology and Molecular Medicine, University of California, Berkeley, USA, Email:

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Description

Tuberculosis (TB), caused predominantly by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, particularly in regions with limited healthcare resources. The pathogenesis of TB hinges on a complex interplay between the bacterium and the host immune system. Understanding these interactions is crucial for developing effective prevention strategies and treatments. TB primarily spreads through airborne transmission, where individuals inhale respiratory droplets containing Mtb. Upon entering the lungs, Mtb encounters alveolar macrophages, the first line of defense. Normally, these macrophages engulf and digest pathogens, but Mtb has evolved mechanisms to evade destruction. Instead, it survives and replicates within these immune cells, establishing a primary infection site. This initial encounter triggers a cascade of immune responses aimed at controlling Mtb's spread.

Adaptive immune response

The adaptive immune response is important for long-term control of TB. Antigen-presenting cells (APCs), particularly dendritic cells, present Mtb antigens to T cells, initiating a specific immune response. CD4⁺ T helper cells, especially Th1 cells, produce cytokines like interferon-gamma (IFN-γ) that activate macrophages to enhance their antimicrobial activity. CD8⁺ cytotoxic T cells also play a role in killing infected cells.

Immune evasion strategies of Mtb

Mtb employs several strategies to evade host immune responses and establish chronic infection. It inhibits phagosome-lysosome fusion within macrophages, preventing acidification and lysosomal enzyme activation. Mtb can also alter its cell wall composition to resist antimicrobial peptides and oxidative stress. Furthermore, it modulates host immune signalling pathways to subvert immune surveillance and promote its survival. Mtb avoids the immune system by preventing its capture by immune cells, altering its cell structure to resist immune attacks, and manipulating immune signals to ensure its survival. Host genetic factors significantly influence TB susceptibility and disease outcomes. Variations in genes encoding immune receptors, cytokines, and other immune regulatory molecules can affect individual immune responses to Mtb. Additionally, co-morbid conditions such as HIV infection, malnutrition, and diabetes weaken host defenses, increasing susceptibility to TB and complicating disease management. Targeted interventions that address specific genetic vulnerabilities and co-morbidities could potentially improve treatment outcomes and reduce transmission rates in endemic areas. Research into hostpathogen interactions continues to inform strategies for better TB control globally.

Implications for treatment and prevention

Effective TB control strategies require a multifaceted approach addressing both bacterial and host factors. Standard treatment involves combination antibiotic therapy (e.g., isoniazid, rifampicin) for six to nine months to eliminate active infection and prevent drug resistance. Vaccines like BCG (Bacillus Calmette-Guérin) offer partial protection against severe forms of childhood TB but are less effective in adults. Additionally, efforts should focus on addressing social determinants of health, such as poverty and malnutrition, which contribute to TB susceptibility. Public education campaigns about TB symptoms, transmission, and the importance of completing treatment are also essential to reduce stigma and improve health-seeking behaviours in affected communities.

Conclusion

The manifestation of TB is intricately linked to the dynamic interactions between Mycobacterium tuberculosis and the host immune system. Understanding these interactions at molecular, cellular, and clinical levels is essential for developing novel diagnostics, therapeutics, and vaccines to combat TB effectively. By elucidating the complexities of TB pathogenesis, we can strive towards global TB elimination goals and alleviate the burden of this ancient disease on public health worldwide.