Researchers from Sweden’s Linköping University discover the pathway that leads to deadly infections in people co-infected with HIV and TB.
As tuberculosis (TB) continues to be one of the top 10 leading causes of death around the world, people co-infected with HIV and TB are at high risk for developing deadly infections. Now, researchers in a new study have found evidence as to why HIV and TB coinfection is such a dangerous combination.
The World Health Organization’s (WHO) recent release of the Global Tuberculosis Report for 2016 offered a grim look at a disease that has infected 10.4 million people worldwide in 2015 and caused 1.8 million deaths. Particularly persistent lung infections associated with the multi-drug resistant forms of TB have, in the past, taken up to 24 months to treat with antibiotics, but better treatment options that are available today can clear those infections in under 12 months. While more easily treatable forms of TB can be cleared within 6 months, for people with HIV, a diagnosis coupled with any form of TB can be critical.
According to WHO, TB is a leading cause of death in people with HIV. In 2015 alone, TB was the cause of 35% of all deaths in HIV-positive people. Of the 1.8 million people who died last year from TB, about 400,000 were co-infected with HIV. The new study, published in The American Journal of Pathology, examined this link between the two diseases. The immune system-depressing effects of HIV make people with the disease more susceptible to life-threatening infections and cancers, and the researchers in this study wanted to understand the mechanism that makes latent TB progress to active TB disease in people with HIV.
"The risk of infection progressing to active tuberculosis is around 30 times higher for people who are HIV-positive. But the reason for this has not been known at the cellular level," said study leader and Senior Lecturer at Sweden’s Linköping University Robert Blomgran in a recent press release.
People who carry Mycobacterium tuberculosis bacteria in their bodies without ever developing illness symptoms have what is called latent TB infection. These people usually have a positive skin or blood test for TB but do not feel sick and cannot spread TB bacteria. Even though they do not feel ill, people with latent TB should be treated to prevent the disease progression. According to the Centers for Disease Control and Prevention, without treatment, about 5% to 10% of people carrying the bacteria will develop TB disease. However, people with HIV are at much greater risk.
To understand why, the study authors looked at dendritic cells, which are antigen-presenting cells that play an important role in immune response. In cases of latent TB, people exposed to the Mycobacterium tuberculosis bacteria are protected by an immune response that surrounds the bacteria in scar tissue. In healthy people, dendritic cells break down the bacteria and push them to the cell surface, where T-cells can bind with the TB bacteria and kill them. The researchers co-infected human dendritic cells with HIV and TB, and they found that the cells had an inhibited immune response and were less able to activate the T-cells needed to kill the bacteria, thus, TB bacteria are more potent in people with HIV.
"We have now shown that HIV has a clear effect also on the innate immune defense, in particular the dendritic cells, which link the innate and the adaptive immune defenses,” explains Dr. Blomgran. “Much work remains to be done, but we can already suggest that one important future treatment strategy for infection should be to find ways to strengthen or boost cells in the immune defense using what is known as 'host-directed therapy'.”