Abstract
Tuberculosis (TB) is a respiratory disease that remains a major cause of morbidity and mortality worldwide. The complexity, poor compliance of patients and poor efficiency of current TB treatments has led to the rise in drug resistant Mycobacterium tuberculosis (Mtb) strains, which pose a significant threat to public health. Harnessing the host immunity against Mtb holds great promises as a therapeutic approach since it can be used against multi-resistant strains and reduces the antibiotics dependency. A key step in the immune response against Mtb is the local containment of the infection by the formation of a granuloma, an agglomerate of immune cells that walls off the pathogen. However, its protection is not always successful since in some cases virulent Mtb (e.g. H37Rv) still disseminates to other organs. Interestingly, an attenuated strain of Mtb (H37Ra) or Mtb strain 18b (Beijing strain that in the absence of streptomycin enters a viable but non-replicating state) do not disseminate out of the lung, suggesting that the host can efficiently contain these strains dissemination. A better understanding of the strain specific containment may provide important targets to be explored in future therapies against TB. Hence, we will gain a novel insight into cell migration and cell-cell interactions responsible for the containment of a Mtb infection by investigating the granuloma formation in a mouse model after infection with Mtb strains with different degrees of local containment. We apply multiphoton intravital microscopy and flow cytometry to establish the steps required to contain the Mycobacterium respiratory infections.
- Copyright ©the authors 2016