The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis.
M. tuberculosis accesses the terminal lung and is phagocytosed by alveolar macrophages. Utilizing a mouse intratracheal challenge model, we demonstrate that M. tuberculosis rapidly enters through M cells as well. From there, bacilli are deposited within associated intraepithelial leukocytes and subsequently conveyed to the draining lymph nodes early after infection. Osteopetrotic (Csfm(op)/Csfm(op)) mice, null mutants for macrophage colony-stimulating factor, possess diminished numbers of circulating monocytes and tissue macrophages. Csfm(op)/Csfm(op) mice were highly susceptible to challenge with M. tuberculosis. In contrast to controls, tubercle bacilli were not conveyed to draining lymph nodes early after infection but were instead retained within the mucosa. These results indicate that M cells represent an alternate portal of entry for M. tuberculosis, which may contribute to the rapid development of protective lung immune responses.
Teitelbaum
R
R
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Schubert
W
W
Gunther
L
L
Kress
Y
Y
Macaluso
F
F
Pollard
J W
JW
McMurray
D N
DN
Bloom
B R
BR
D000818:Animals; D001980:Bronchi / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology / Q000648:ultrastructure; D005260:Female; D020022:Genetic Predisposition to Disease / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity* / Q000648:ultrastructure; D010022:Osteopetrosis / Q000235:genetics / Q000382:microbiology; D013997:Time Factors; D014376:Tuberculosis / Q000382:microbiology / Q000401:mortality / Q000473:pathology*