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 demonstrat e that M. tuberculosis rapidly enters through M cells as well. From there, bacilli are deposited within associated intraepithelial leukocytes and subs equently conveyed to the draining lymph nodes early after infection. Osteop etrotic (Csfm(op)/Csfm(op)) mice, null mutants for macrophage colony-stimul ating factor, possess diminished numbers of circulating monocytes and tissu e macrophages. Csfm(op)/Csfm(op) mice were highly susceptible to challenge with M. tuberculosis. In contrast to controls, tubercle bacilli were not co nveyed to draining lymph nodes early after infection but were instead retai ned within the mucosa. These results indicate that M cells represent an alt ernate portal of entry for M. tuberculosis, which may contribute to the rap id development of protective lung immune responses.