Summary

This work is relevant because it highlights an important aspect that is still often underestimated in tuberculosis research: the genetic background of the infecting M. tuberculosis strain can strongly influence the host response. Many studies are still mainly based on laboratory reference strains, particularly H37Rv, but these strains do not necessarily reproduce the behaviour of the different clinical lineages circulating in the population. By comparing strains with different genetic backgrounds in different macrophage activation states, we show that host–pathogen interactions are highly variable and that processes such as phagosomal acidification depend on both the bacterial strain and the host cell phenotype. This is particularly important when studying host adaptation and immune evasion, but also from a translational point of view, since results obtained using only H37Rv may not always be representative of the response to clinical strains and could influence the evaluation of host-directed therapies.