Mycobacterial infection of macrophages results in membrane-permeable phagosomes

R. Teitelbaum, M. Cammer, M. L. Maitland, N. E. Freitag, John S. Condeelis, B. R. Bloom

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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 la 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.

Original languageEnglish (US)
Pages (from-to)15190-15195
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number26
DOIs
StatePublished - Dec 21 1999

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Phagosomes
Major Histocompatibility Complex
Macrophages
Membranes
Infection
Mycobacterium
Antigens
Cytoplasm
T-Lymphocytes
Ovalbumin
Infection Control
Vacuoles
Green Fluorescent Proteins
Dextrans
Mycobacterium tuberculosis
Confocal Microscopy
Cellular Immunity
Tuberculosis
Communication
Food

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mycobacterial infection of macrophages results in membrane-permeable phagosomes. / Teitelbaum, R.; Cammer, M.; Maitland, M. L.; Freitag, N. E.; Condeelis, John S.; Bloom, B. R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 26, 21.12.1999, p. 15190-15195.

Research output: Contribution to journalArticle

Teitelbaum, R. ; Cammer, M. ; Maitland, M. L. ; Freitag, N. E. ; Condeelis, John S. ; Bloom, B. R. / Mycobacterial infection of macrophages results in membrane-permeable phagosomes. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 26. pp. 15190-15195.
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