Mycobacterial infection of macrophages results in membrane-permeable phagosomes.
Cell-mediated immunity is critical for host resistance to tuberculosis. T lymphocytes recognizing antigens presented by the major histocompatibility complex (MHC) class I and class II molecules have been found to be necessary for control of mycobacterial infection. Mice genetically deficient in the generation of MHC class I and class Ia responses are susceptible to mycobacterial infection. Although soluble protein antigens are generally presented by macrophages to T cells through MHC class II molecules, macrophages infected with Mycobacterium tuberculosis or bacille Calmette-Guerin have been shown to facilitate presentation of ovalbumin through the MHC class I presentation pathway via a TAP-dependent mechanism. How mycobacteria, thought to reside within membrane-bound vacuoles, facilitate communication with the cytoplasm and enable MHC class I presentation presents a paradox. By using confocal microscopy to study the localization of fluorescent-tagged dextrans of varying size microinjected intracytoplasmically into macrophages infected with bacille Calmette-Guerin expressing the green fluorescent protein, molecules as large as 70 kilodaltons were shown to gain access to the mycobacterial phagosome. Possible biological consequences of the permeabilization of vacuolar membranes by mycobacteria would be pathogen access to host cell nutrients within the cytoplasm, perhaps contributing to bacterial pathogenesis, and access of microbial antigens to the MHC class I presentation pathway, contributing to host protective immune responses.
Teitelbaum
R
R
Department of Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cammer
M
M
Maitland
M L
ML
Freitag
N E
NE
Condeelis
J
J
Bloom
B R
BR
D000818:Animals; D017951:Antigen Presentation; D001427:Bacterial Toxins; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000382:microbiology*; D002451:Cell Compartmentation; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D008089:Listeria monocytogenes / Q000472:pathogenicity; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D008970:Molecular Weight; D009161:Mycobacterium / Q000276:immunology / Q000472:pathogenicity*; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity; D020102:Mycobacterium smegmatis / Q000276:immunology / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D010539:Permeability; D010588:Phagosomes / Q000502:physiology*
D001427:Bacterial Toxins; D015415:Biomarkers; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; C038705:hlyA protein, Listeria monocytogenes