Studies of human tuberculosis have been hampered by the lack of an in vitro model that recapitulates all the features of a natural infection with Mycobacterium tuberculosis. This paper describes a unique combination of in vitro culture conditions that enables the generation of human monocyte-derived macrophages (MDMs) that can survive infection with M. tuberculosis and control its replication for more than 2 weeks. The new protocol involves monocyte culture for 2 weeks at 10% oxygen in 40% human plasma containing the cytokines GM-CSF and TNF, with the medium replaced every 3–4 days, followed by 'activation' with interferon-γ for 2 days prior to infection. The authors showed that culture in fetal bovine serum or with M-CSF (two additives that are commonly used for the culture of human monocytes) led to the generation of MDMs that were unable to control M. tuberculosis replication and died.
ORIGINAL RESEARCH PAPER
Vogt, G. & Nathan, C. In vitro differentiation of human macrophages with enhanced antimycobacterial activity. J. Clin. Invest. 121, 3889–3901 (2011)
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Recapitulating human TB in vitro. Nat Rev Immunol 11, 716 (2011). https://doi.org/10.1038/nri3105
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DOI: https://doi.org/10.1038/nri3105