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How HIV infection increases the risk of tuberculosis

One in three people world-wide are thought to be infected with Mycobacterium tuberculosis (Mtb), but most remain well because their immune system keeps the pathogen in check. HIV infection dramatically increases the risk of Mtb infection turning into active tuberculosis (TB), a life-threatening disease. Exactly how HIV infection affects the immune system’s ability to suppress active TB is still poorly understood.

A study published in PLOS Pathogens suggests that it is not a general weakening of the immune system by HIV that initially leads to loss of Mtb control, but rather that HIV is associated with a failure to prevent harmful immune responses. As HIV disease progresses, the weakening immune system’s focus on antiviral responses leaves it largely defenseless against the Mtb pathogen.

Mahdad Noursadeghi, from University College London, UK, and colleagues, performed a detailed analysis of the immune response to Mtb in individuals at different stages of HIV infection. They used the standard tuberculin skin test (TST), a sterile injection of purified Mtb proteins into the forearm skin, and then measured the activity of all possible genes in the injection-site tissue of volunteer participants 48 hours later, to characterize the immune response in comprehensive detail.

The researchers started with HIV-negative volunteers who had active TB, and found a specific TST gene signature produced in response to the injection. They then compared the TST signature with published gene expression profiles from active TB disease sites in the lung, as well as with gene expression patterns in the circulating blood from active TB patients. They found that the gene expression changes within the TST more accurately reproduced the molecular patterns at the site of active TB than the changes in peripheral blood, and used this to quantify immune cell recruitment and a wide range of other specific immune responses.

Exaggerated IRF4 expression associated with Th2 immunity in tuberculin skin tests of HIV infected TB-IRIS patient]
Exaggerated IRF4 expression associated with Th2 immunity in tuberculin skin tests of HIV infected TB-IRIS patients
Image Credit: Lucy Bell, University College London