Voortgezette Celbiologie Evelien Floor
Mycobacterium tuberculosis
Mycobacterium tuberculosis (TB) is still the number one pathogen killing the most people in the
world, more than HIV and malaria. Nowadays antibiotics are available to treat tuberculosis but the
resistance for antibiotics is a big threat. Already 75.000 cases of multidrug resistance TB cases were
reported in the EU. Extreme drug resistance (XDR) means no medication is available to treat you
anymore. In the case of MDR there are still possibilities for medication.
Antigen presentation on MHC class II molecules
Processing of intact exogenous antigen and peptide vaccines is similar, and both are loaded onto the
major histocompatibility complex (MHC) class II molecules. Similar to MHC-I-targeted epitopes,
peptide antigens can access surface MHC II molecules and replace existing peptides by a surface-
exchange mechanism (a). Exogenous antigen and peptide vaccines are taken up into the endosomal
pathway by macropinocytosis or by receptor-mediated events (b). Once the intact antigen or peptide
enters the endocytic compartment they are exposed to various proteases which are responsible for
antigen degradation (c). Peptide vaccines therefore need to survive this environment as they are
transported to a compartment known as MIIC (an MHC-II-rich endosomal compartment). Here
peptides are loaded into MHC II molecules, a process that is facilitated by the chaperone human
leukocyte antigen-DM (HLA-DM) (d).
Once the MHC class II molecule is loaded they travel to the plasma membrane. Once a cell is infected
the lysosomes (MIIC) travel as fast as they can to the membrane to present the antigen peptides.
M. tuberculosis survives in the cell
For a long time, people thought that bacteria could avoid going from the phagosome to the
lysosome. But in fact, lysosomes dump their content into the phagosome. In the case of M.
tuberculosis, it is able to move to the cytosol after a few days.
M. tuberculosis rapidly acquires lysosomal characteristics because only 2 hours after infection
lysosomes start to fuse with phagosomes forming phagolysosomes. The environment of the
phagosome will become more acid and enzymes for proteolysis are added too. M. tuberculosis is
located in the phagolysosome after 2 hours and 4 hours. After 48 hours, M. tuberculosis is still
located in the phagolysosome but also in the cytosol. Fluorescence images of dendritic cells infected
with M. tuberculosis show that after 96 hours the bacteria are not colocalized with lysosomal
markers (LAMP-1) anymore. This all indicates that after approximately 48 hours M. tuberculosis is
able to exit the phagolysosome.
1
Mycobacterium tuberculosis
Mycobacterium tuberculosis (TB) is still the number one pathogen killing the most people in the
world, more than HIV and malaria. Nowadays antibiotics are available to treat tuberculosis but the
resistance for antibiotics is a big threat. Already 75.000 cases of multidrug resistance TB cases were
reported in the EU. Extreme drug resistance (XDR) means no medication is available to treat you
anymore. In the case of MDR there are still possibilities for medication.
Antigen presentation on MHC class II molecules
Processing of intact exogenous antigen and peptide vaccines is similar, and both are loaded onto the
major histocompatibility complex (MHC) class II molecules. Similar to MHC-I-targeted epitopes,
peptide antigens can access surface MHC II molecules and replace existing peptides by a surface-
exchange mechanism (a). Exogenous antigen and peptide vaccines are taken up into the endosomal
pathway by macropinocytosis or by receptor-mediated events (b). Once the intact antigen or peptide
enters the endocytic compartment they are exposed to various proteases which are responsible for
antigen degradation (c). Peptide vaccines therefore need to survive this environment as they are
transported to a compartment known as MIIC (an MHC-II-rich endosomal compartment). Here
peptides are loaded into MHC II molecules, a process that is facilitated by the chaperone human
leukocyte antigen-DM (HLA-DM) (d).
Once the MHC class II molecule is loaded they travel to the plasma membrane. Once a cell is infected
the lysosomes (MIIC) travel as fast as they can to the membrane to present the antigen peptides.
M. tuberculosis survives in the cell
For a long time, people thought that bacteria could avoid going from the phagosome to the
lysosome. But in fact, lysosomes dump their content into the phagosome. In the case of M.
tuberculosis, it is able to move to the cytosol after a few days.
M. tuberculosis rapidly acquires lysosomal characteristics because only 2 hours after infection
lysosomes start to fuse with phagosomes forming phagolysosomes. The environment of the
phagosome will become more acid and enzymes for proteolysis are added too. M. tuberculosis is
located in the phagolysosome after 2 hours and 4 hours. After 48 hours, M. tuberculosis is still
located in the phagolysosome but also in the cytosol. Fluorescence images of dendritic cells infected
with M. tuberculosis show that after 96 hours the bacteria are not colocalized with lysosomal
markers (LAMP-1) anymore. This all indicates that after approximately 48 hours M. tuberculosis is
able to exit the phagolysosome.
1
