Dr Leopold Tientcheu compares human host responses between TB patients infected with Maf and Mtb

The publication, entitled “Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before drug treatment” appeared in July/August issue of Gene and Immunity, which is one of Nature’s publish group journals.

This study is among the first in West Africa to compare human host responses between tuberculosis (TB) patients infected with Mycobacterium africanum (Maf) and Mycobacterium tuberculosis (Mtb) at a global level using clinical data and high-throughput techniques.

Dr Leopold TientcheuThe research work contained in this publication, was part of the MRC-funded PhD training fellowship awarded to Dr Leopold Tientcheu Djomkam, who is the first author of this publication. This research work was nested within the MRC-Tuberculosis Case Contact (TBCC) platform, under which all the study patients were recruited. The transcriptomic and metabolomics analysis were done through a collaboration with Professor Stefan Kaufmann’s Lab at the Max Planck Institute for Infection Biology, Berlin, Germany.

In The Gambia, Mtb and Maf are the two main lineages causing TB. The proportion of with immune suppression was higher amongst patients with Maf infection compared to Mtb-infected, implying differences in the virulence of the two strains. In order to identify host biomarkers associated with strain-specific pathogenesis and response to anti-TB chemotherapy, we compared the clinical presentation, peripheral blood gene expression and serum metabolic profiles, before and after treatment between patients infected with either of the two strains.

Both groups of patients displayed very similar gene expression and metabolic profiles at baseline, reflecting similar clinical presentation before treatment. Changes over the time of treatment were comparable in both groups, but more pronounced in Mtb-infected patients who also displayed better clinical recovery post treatment. We observed over 1600 genes related to immune responses and metabolic diseases differentially expressed between the two groups, after the completion of the standard anti-TB treatment. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. These results suggest a possible underlying effect of systemic metabolism, affecting the susceptibility and clinical resolution of TB disease in Maf-infected patients.

“This study highlights the differences, existing between TB patients infected by different MTBC strains that was overlooked before. The fact that differences between the two groups appear only after treatment implies that, it is not sufficient to study the strains effect at just one time point (e.g before treatment) as the disease process might overshadow strains-specific effects. The responses observed post treatment warrant further investigation, especially in this era of TB research, where host-directed therapy is gaining more interest. Understanding the contribution of MTBC strains in the complex host-pathogen interaction, would help us to develop better tools to control TB. We are currently exploring how the post-treatment profiles of Maf- and Mtb-infected patients might affect their long-term recovery from disease”.