Modulating host macrophage functions to control latent tuberculosis - using helminth coinfection in high-endemic areas as a model

This project focuses on how chronic helminthic worm infections impair immune control of human tuberculosis (TB), and how current treatment strategies could be optimized to shorten duration of anti-TB chemotherapy, and protect those at risk for developing active disease.

We have shown that coinfection with intestinal helminthic parasites can impair efficient TB-protection by suppressing bactericidal functions in macrophages (MQ), triggering progression from latent to active TB disease.

Our previous results also show that nutritional deficiencies in the nitric oxide (NO) and glutathione axis may contribute to poor control of mycobacteria by human MQ.

Using a translational approach combining clinical TB studies (Ethiopia) with ex vivo infection experiments we will determine if L-citrulline administration can revert the effect of chronic helminth infection in MQ by switching them from their immunosuppressed regulatory M2 phenotype to a proinflammatory M1 phenotype and simultaneously trigger enhanced NO production, to achieve better host control of mycobacteria.

How helminthic infection impairs macrophage activation will be studied in individuals with latent TB with/without concurrent helminth infection, before and after deworming.

Our research will show if adjunctive immune boosting therapies that strengthens and activates macrophages can expedite current anti-TB treatment, and if interventions like deworming could be beneficial for individuals living in low resource areas.