Tuberculosis (TB) is a serious infectious disease primarily affecting the lungs, though it can also impact other parts of the body like the kidneys, spine, and brain. It is caused by the bacterium Mycobacterium tuberculosis. While TB is not directly inherited, an individual’s genetic makeup can influence their susceptibility to developing the disease after exposure or how their body responds to the infection.
How Tuberculosis Spreads
Tuberculosis spreads through the air when a person with active TB disease in their lungs or throat expels tiny particles containing Mycobacterium tuberculosis bacteria. This occurs when an infected individual coughs, sneezes, sings, or speaks, releasing microscopic droplets. Others can then inhale these droplets, leading to potential infection. Transmission generally requires prolonged, close contact in shared air spaces.
TB is not spread through casual contact, such as shaking hands, sharing eating utensils, or touching surfaces. The bacteria cannot survive long on surfaces and must be inhaled to cause infection. While exposure is necessary, not everyone exposed will become infected.
Genetic Factors in TB Susceptibility
While Mycobacterium tuberculosis is the direct cause of tuberculosis, variations within an individual’s genes can significantly influence their immune system’s ability to combat the bacteria. These genetic differences do not cause TB itself but rather modulate how effectively a person’s body responds to the infection. Specific genes involved in the innate and adaptive immune responses have been identified as playing a role in determining susceptibility or resistance to TB progression. For instance, genes that regulate the production of cytokines, signaling proteins that control immune cell activity, can alter the body’s inflammatory response to the bacteria.
Genetic variations in pathways related to macrophage function, the immune cells that initially engulf and attempt to destroy the bacteria, can also affect the outcome of an infection. Polymorphisms in genes such as NRAMP1 (now known as SLC11A1), involved in macrophage defense against intracellular pathogens, have been linked to varying risks of developing active TB. Similarly, genes influencing T-cell responses, crucial for long-term immunity against Mycobacterium tuberculosis, can dictate how well the immune system contains the bacteria or clears the infection.
Environmental and Individual Risk Factors
Beyond genetic predispositions, numerous environmental and individual factors influence the risk of developing TB infection and progressing to active disease. Prolonged and close contact with someone who has active, infectious TB is a primary risk factor, as it increases the likelihood of inhaling the bacteria. Living in crowded or poorly ventilated environments can facilitate airborne transmission, making it easier for the bacteria to spread among individuals. These conditions are often found in settings with limited resources, contributing to higher incidence rates.
A weakened immune system is another major contributor to TB susceptibility and progression. Conditions such as HIV/AIDS, which severely compromise the immune system, increase the risk of developing active TB. Other health issues like diabetes, chronic kidney disease, certain cancers, and treatments involving immunosuppressive medications can also impair the body’s ability to fight off the Mycobacterium tuberculosis bacteria. Lifestyle choices, including malnutrition, weakening overall bodily defenses, and excessive smoking or alcohol abuse, compromising lung health and immune function, further elevate the risk. Very young children and older adults are also more vulnerable due to their developing or declining immune systems.
Latent vs. Active TB: Why Some Get Sick
Upon exposure to Mycobacterium tuberculosis, an individual can develop either a latent TB infection (LTBI) or active TB disease, with the outcome dependent on their immune response. In latent TB infection, the bacteria enter the body but remain inactive, contained by the immune system. Individuals with LTBI have no symptoms and cannot spread the bacteria to others, as their immune defenses contain the microbes. This state can persist for years.
Active TB disease, in contrast, occurs when Mycobacterium tuberculosis bacteria multiply and overcome the immune system’s containment efforts. This leads to symptoms such as a persistent cough, fever, night sweats, and weight loss, and the infected person becomes capable of transmitting the disease. The progression from latent infection to active disease is often triggered by a weakened immune system, which can result from genetic predispositions, co-existing health conditions like HIV, or environmental stressors such as malnutrition. The interplay of these factors ultimately determines whether an exposed individual’s immune system can maintain bacterial containment or if the infection will progress to symptomatic illness.
References
https://www.cdc.gov/tb/topic/basics/howtbspreads.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059045/