Download Mycobacterium tuberculosis interactions with host cells

Mycobacterium tuberculosis interactions with host cells
Olivier Neyrolles
Institut de Pharmacologie et de Biologie Structurale, Toulouse, France
One of the key features rendering the tubercle bacillus highly virulent is its ability to
parasitize host phagocytic cells, including macrophages and dendritic cells in particular. The
molecular mechanisms involved in this process have only recently been investigated, as well
as host cell responses to M. tuberculosis infection, together with the microbial factors
involved in intracellular survival.
I will discuss recent findings in the field, made by our laboratory and others.
In particular, we have used high-content visual analysis of a genome-covering M. tuberculosis
mutant library screened at the whole cell and organelle levels in macrophages to identify a
number of novel microbial genes involved in mycobacterial intracellular trafficking and host
cell parasitism. A novel locus involved in the synthesis and export of particular lipids of the
mycobacterial cell envelope has been identified. In addition, a recent global profiling study of
host cell and mycobacterial responses to infection has allowed to identify several families of
eukaryotic and microbial genes whose expression is modulated upon infection. In particular
the expression of host cell and mycobacterial genes encoding various intracellular solute
carriers has been found to be strongly altered during the infection process. The role of
selected members of these transporter families in host-pathogen interactions is currently under
investigation.
Finally, we have identified the C-type lectin DC-SIGN as a key M. tuberculosis receptor on
the dendritic cells and alveolar macrophages of patients with TB. We have recently furthered
our understanding of the role of DC-SIGN in TB, by investigating the function of selected
mouse DC-SIGN homologues in experimental TB in mice, using various in vivo and in vitro
systems. We showed that the DC-SIGN murine homologue SIGNR3 mediates early
protection against M. tuberculosis, through recognition of sugar motifs in the mycobacterial
cell envelope and induction of protective cytokine secretion. C-type lectins and other
mediators of innate and adaptive immunity.