Understanding the role of the cell surface molecule CD153 in TB protection
1 Aug 2019 - 11:45
CIDRI-Africa contributing investigator Dr Catherine Riou has been awarded a two-year National Institutes of Health (NIH) R21 grant to investigate immune responses to Mycobacterium tuberculosis (Mtb) in the context of HIV infection. This work will be performed in collaboration with Dr Elsa du Bruyn, Associate Prof. Maia Lesosky and Prof. Robert J Wilkinson, co-investigators on the project.
In 90% of cases, healthy people who are infected with Mtb never develop symptoms of tuberculosis. This implies that the human body can generate and maintain a partially protective immune response capable of containing bacterial replication. When this equilibrium is altered, such as during HIV-associated CD4 T cell depletion, TB disease can occur.
However, the precise nature of Mtb-specific CD4 T cells that confer immune protection remains unclear. Recent findings showed that CD4 T cells expressing the TNF superfamily molecule CD153 conferred partial protection against pulmonary Mtb infection in a mouse model.
CIDRI-Africa investigators have found that the expression of CD153 on Mtb-specific CD4 T cells correlated with TB disease state in humans, where the expression of this molecule was significantly reduced in patients with active TB disease when compared with latently infected persons. These findings strongly suggest that CD153 may be in part required to confer optimal protection against pulmonary Mtb infection in humans.
Under this award Catherine’s team will:
comprehensively characterize Mtb-specific CD153+ CD4 T cells during latent and active TB, both in peripheral blood and at sites of TB diseases;
define the impact of HIV infection on Mtb-specific CD4 T cells expressing CD153; and
investigate the mechanisms of action of the CD153/CD30 pathway in response to Mtb to better understand the role of CD153 (and its receptor, CD30) in Mtb protection.
Their research will enhance our understanding of immune mechanisms required for human TB protection and identify novel mechanisms by which HIV infection alters these immune responses. This project complements Catherine’s EDCTP Senior Fellowship programme of work, and could lead to the development of new tools for TB diagnosis and to monitor the efficacy of novel TB vaccines.