When people suffer from both HIV and TB, it creates “one of the biggest health problems in the world,” according to Texas Biomed Assistant Professor Smita Kulkarni, Ph.D. Now, the National Institutes of Health is funding a two-year study by Texas Biomed scientists developing a lab model that mimics the early stages of the co-infection of these two diseases.
HIV-infected patients are 30 times more likely to develop active tuberculosis than people without HIV. TB — caused by infection with M. tuberculosis bacteria — is the leading cause of death among HIV patients. In Africa and Asia, where TB is more prevalent, patients tend to acquire the lung disease first, and then contract HIV, the virus that causes AIDS. In the United States, patients with HIV tend to develop active TB at higher rates later in life.
Co-infection with HIV and TB “leads to worse control of both pathogens, faster death and a greater impact on society, since chances of other people being exposed to TB are greater,” Dr. Kulkarni explained.
When people are infected with TB, immune cells surround the invading bacteria and form what are called granulomas – a mass of cells that include macrophages and lymphocytes. This is the body’s attempt to wall off the infection. However, latent TB, which suppresses symptoms and transmissibility, can turn into active TB later, leading to clinical disease. HIV is found in these granulomas in co-infected individuals, yet “No one has tried to recapitulate this complex interaction in a lab setting.”
By creating a granuloma in a petri dish, “we can see granulomas in the earliest stages and ask formative questions about what’s happening,” Staff Scientist Eusondia Arnett, Ph.D., said. “For instance, how does HIV infection alter granuloma development and function, and what factors are at play? What host molecules are not functioning correctly at this stage to allow the infections to get worse?”
Once this innovative laboratory model has been characterized and the base mechanisms of cell interaction are more fully understood, Texas Biomed scientists say the model could be used as a less expensive, faster, and perhaps more accurate model to conduct initial tests on experimental treatments for both HIV and TB than animal models.
Working at an infectious disease institute with teams of experts in different fields has been “critical,” according to Dr. Arnett. “As TB researchers, we would not be able to conduct this kind of study without experts in the field of HIV.”
UT Health San Antonio will also be involved in the study, providing expertise in laser capture of granulomas and single cell analysis.
Work on the study began this spring. Scientists plan on publishing early results soon.
Dr. Kulkarni and Texas Biomed President Dr. Larry Schlesinger are Principal Investigators.
This research is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R21 AI145539.