Induction of TNF in human alveolar macrophages as a potential evasion mechanism of virulent Mycobacterium tuberculosis.
The ability of macrophages to release cytokines is crucial to the host response to intracellular infection. In particular, macrophage-derived TNF plays an important role in the host response to infection with the intracellular pathogen Mycobacterium tuberculosis. In mice, TNF is indispensable for the formation of tuberculous granulomas, which serve to demarcate the virulent bacterium. TNF is also implicated in many of the immunopathological features of tuberculosis. To investigate the role of TNF in the local immune response, we infected human alveolar macrophages with virulent and attenuated mycobacteria. Infection with virulent strains induced the secretion of significantly higher levels of bioactive TNF than attenuated strains correlating with their ability to multiply intracellularly. Treatment of infected macrophages with neutralizing anti-TNF Abs reduced the growth rate of intracellular bacteria, whereas bacterial replication was augmented by addition of exogenous TNF. Infected and uninfected macrophages contributed to cytokine production as determined by double-staining of M. tuberculosis and intracellular TNF. The induction of TNF by human alveolar macrophages at the site of infection permits the multiplication of intracellular bacteria and may therefore present an evasion mechanism of human pathogens.
Engele
Matthias
M
Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Friedrich-Alexander Universität Erlangen-Nürnberg, Wasserturmstrasse 3, D-91054 Erlangen, Germany.
Stössel
Elmar
E
Castiglione
Kirstin
K
Schwerdtner
Nives
N
Wagner
Manfred
M
Bölcskei
Pal
P
Röllinghoff
Martin
M
Stenger
Steffen
S
D001500:BCG Vaccine / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D012995:Solubility; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D014613:Vaccines, Attenuated / Q000494:pharmacology; D014774:Virulence
D001500:BCG Vaccine; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated