A new publication in Nature Communications explains how T cell protection against tuberculosis is controlled by their oxygen responses.
In 2021, 10 million people fell ill and 1.5 million died of Tuberculosis (TB), caused by infection with the intracellular Mycobacterium tuberculosis bacteria. Proper CD4 T cell responses are critical for the control of M. tuberculosis infection by activating intracellular bacterial killing.
Professor Martin Rottenberg and PhD student Ruining Liu at the Karolinska Institutet, explained how they discovered that hypoxia-inducible factors (HIF-1 and HIF-2) control T cell metabolism as well as activation and differentiation in response to hypoxia or during inflammation.
“We showed that genetically modified mice, in which HIF-1 expression T cells was stabilised by genetic manipulation, were highly susceptible to the infection with M. tuberculosis and did not respond to vaccination. CD4 T cells from these mice were profoundly weakened in their early responses to mycobacteria-specific antigens, said Prof Rottenberg. “By impairing and or controlling HIF-1 stabilisation in T cells, responses to vaccines and protection against infections might be improved”.
The studies were carried out on mouse models of M. tuberculosis infection. The mice used were genetically modified to either lack or overexpress HIF-1 in T cells.
“The infection with M. tuberculosis, and the immune responses it generates in man, is fairly mimicked in the mouse infection. Our next step is to identify the molecular targets HIF-1 in T cells that account for their impaired activation, which could be targeted for improving T cell responses,” Prof Rottenberg concluded.
Source: Karolinska Institutet
