ABOUT

The group Host Targets of Infection (HoTI) investigates the impact of chronic infection on host homeostasis, with a special interest on Non-Tuberculous Mycobacteria (NTM). Using in vitro models, animal experiments and human studies, it contributes to the elucidation of mechanisms of disease, as well as to the development of both host-targeted and microbe-targeted drugs.

RESEARCH

Regarding the impact of chronic infection on host homeostasis, we are especially interested in iron-related alterations. We found that infections by mycobacteria cause a notorious iron re-distribution in the host. The inflammatory mediators released during infection, namely interferon gamma (IFNG), cause defective erythropoiesis, leading to the formation of red blood cells with a decreased life span. Increased red blood cell destruction leads to intra-macrophagic iron accumulation and oxidative stress, contributing to pathology. In this context, the iron-binding capacity of H-ferritin exerts an important protective effect.

Iron withholding plays a key role in the host’s protection against infection, but other mechanisms are also important. Macrophages and neutrophils produce several molecules with significant antimicrobial activity, namely antimicrobial peptides (AMP). AMP derived from lactoferrin can inhibit the growth of mycobacteria, both through direct mechanisms and through the modulation of the antimicrobial activity of macrophages. The HoTI group is working on the optimization of AMP and other anti-mycobacterial molecules, for future therapeutic use. For this, we have optimized drug screening assays, based on fluorescent and luminescent strains of M. avium and M. abscessus, encompassing simple direct activity on planktonic bacteria, but also biofilm and macrophage infection models.