Chlamydia trachomatis vacuole maturation in infected macrophages.
Chlamydia trachomatis is an obligate intracellular bacterium responsible for one of the most common sexually transmitted diseases. In epithelial cells, C. trachomatis resides in a modified membrane-bound vacuole known as an inclusion, which is isolated from the endocytic pathway. However, the maturation process of C. trachomatis within immune cells, such as macrophages, has not been studied extensively. Here, we demonstrated that RAW macrophages effectively suppressed C. trachomatis growth and prevented Golgi stack disruption, a hallmark defect in epithelial cells after C. trachomatis infection. Next, we systematically examined association between C. trachomatis and various endocytic pathway markers. Spinning disk confocal time-lapse studies revealed significant and rapid association between C. trachomatis with Rab7 and LAMP1, markers of late endosomes and lysosomes. Moreover, pretreatment with an inhibitor of lysosome acidification led to significant increases in C. trachomatis growth in macrophages. At later stages of infection, C. trachomatis associated with the autophagy marker LC3. TEM analysis confirmed that a significant portion of C. trachomatis resided within double-membrane-bound compartments, characteristic of autophagosomes. Together, these results suggest that macrophages can suppress C. trachomatis growth by targeting it rapidly to lysosomes; moreover, autophagy is activated at later stages of infection and targets significant numbers of the invading bacteria, which may enhance subsequent chlamydial antigen presentation.
Departments of Cell and Systems Biology and Biological Sciences, University of Toronto Scarborough, Ontario, Canada.
He Song
HS
Sun
Edward W Y
EW
Eng
Sujeeve
S
Jeganathan
Alex T-W
AT
Sin
Prerna C
PC
Patel
Eric
E
Gracey
Robert D
RD
Inman
Mauricio R
MR
Terebiznik
Rene E
RE
Harrison
D000818:Animals; D001343:Autophagy; D002692:Chlamydia trachomatis / Q000254:growth & development*; D004847:Epithelial Cells / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis; D014617:Vacuoles / Q000382:microbiology*; D020691:rab GTP-Binding Proteins / Q000502:physiology; D020696:rab5 GTP-Binding Proteins / Q000502:physiology; D000090802:rab7 GTP-Binding Proteins
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins