Tobacco smoking, and exposure to smoke, increases the risk for developing tuberculosis, an infectious disease that kills a large number of people every year. Indeed, according to the World Health Organization (WHO), in 2014, tuberculosis—or TB for short—killed 1.5 million people worldwide (1.1 million HIV-negative and 0.4 million HIV-positive). The toll comprised 890,000 men, 480,000 women, and 140,000 children. TB now ranks alongside HIV as a leading cause of death worldwide—HIV’s death toll in 2014 was estimated at 1.2 million, which included the 0.4 million TB deaths among HIV-positive people. In other words, as discussed by Joanne Carter in the Opinion Pages of the New York Times, we have allowed a preventable, curable disease to become the world’s biggest communicable killer.
Carter says that we’ve been very successful at curing people of TB since the 1950s, so she asks: why is this illness still such a scourge? The answer she gives is that TB is an airborne infectious disease. If untreated, one person with TB can infect 10 to 15 others in the space of a year. The existing vaccine is largely ineffective, and there is no simple test where most people first get care. Drug-resistant strains of Mycobacterium tuberculosis, the microorganism that causes this disease, continue to spread, far outpacing the development of new drugs. In addition, the treatment for drug-resistant TB can be grueling, with sometimes devastating side effects. “These challenges are real, but the biggest problem we face with tuberculosis is not scientific. It’s political. TB has climbed up the list of major killers worldwide, but it’s stuck at the bottom of the list of political priorities.”
She adds: “We have the means to cure an overwhelming majority of people sick with TB. And thanks to recent breakthroughs in molecular-based tests, we can now diagnose and start to treat patients faster. But these things alone won’t be enough. We need the tools to get ahead of the epidemic, not just struggle to keep up, and we need the global investment to get the best diagnostics and the right treatment to the people who need them most.”
In the mean time, researchers continue to elucidate the mechanisms that allow M. tuberculosis to cause disease. In 2014, a group of scientists in Taiwan published a study showing that regular tobacco smoking doubles the risk that people who have been successfully treated for TB will develop the disease again—a condition known as recurrent tuberculosis. Chung-Yeh Deng, one of the study authors, said: “More than ever before, we understand how tobacco harms people who have already been successfully treated for TB. No one should undergo the long, complex treatment for TB only to unknowingly place themselves at heightened risk of getting the disease again. With this research we can inform national tobacco control policies and educate patients about the risks that smoking tobacco poses.”
Now, results from a recently published study (Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration) explain why smokers, and people exposed to smoke, are at increasing risk of developing tuberculosis: smoking causes a type of immune cells—the macrophages—to become clogged up. What happens when the macrophages become clogged up? They move slowly, and lose their ability to fight M. tuberculosis.
When M. tuberculosis enters the lungs, the first line of defense it encounters is the macrophage—the “big eater“. Macrophages migrate to the site of infection, engulf M. tuberculosis, and try to break it down. In many cases, macrophages are successful and kill M. tuberculosis, preventing TB infection. However, in some cases, M. tuberculosis manages not just to avoid destruction, but to use macrophages as “taxi cabs” and get deep into the host, spreading the infection and causing infected macrophages to form tightly organized clusters known as tubercles, or granulomas. Within the granulomas, the macrophages and bacteria fight a battle—if the macrophages lose, the bacteria spread from cell to cell.
In addition to fighting invading microbes, macrophages have a very important “housekeeping” function—they recycle unwanted material from within the body for reuse. The researchers found that macrophages clogged up with smoke particles did not migrate efficiently, and could not respond to infection— therefore, they’re defective macrophages. Lalita Ramakrishnan, senior author of the study, said in a press release: “Macrophages act a bit like vacuum cleaners, hoovering up debris and unwanted material within the body, including the billions of cells that die each day as part of natural turnover. But the defective macrophages are unable to recycle this debris and get clogged up, growing bigger and fatter and less able to move around and clear up other material.”
Joe Keane, one of the study co-authors, said in the same press release: “Macrophages are our best shot at getting rid of TB, so if they are slowed down by smoke particles, their ability to fight infection is going to be greatly reduced. We know that exposure to cigarette smoke or smoke from burning wood and coal, for example, are major risk factors for developing TB, and our finding helps explain why this is the case. The good news is that stopping smoking reduces the risk—it allows the impaired macrophages to die away and be replaced by new, agile cells.”
Indeed, the researchers found that ex-smokers have significantly fewer defective macrophages than smokers In addition, in ex-smokers, the ability of macrophages to migrate to M. tuberculosis was restored. In their paper, the researchers conclude that their findings provide an additional rationale for smoking cessation as a prescription for TB prevention.