Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo

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Science Immunology  26 Jul 2019:
Vol. 4, Issue 37, eaaw6693
DOI: 10.1126/sciimmunol.aaw6693

Interfering with macrophage activation

One of the many reasons for Mycobacterium tuberculosis (M.tb.) persistence is that the bacterium blocks activation of M.tb.-specific immune responses. Here, using a mouse model of tuberculosis, Rothchild et al. demonstrate that M.tb.-infected alveolar macrophages in the lung show an impaired ability to drive antibacterial responses. These M.tb.-infected macrophages up-regulate an antioxidant transcription signature that is driven by the transcription factor nuclear factor erythroid 2–related factor 2 (NRF2). By infecting mice engineered to lack NRF2 in myeloid cells with M.tb., they show that loss of NRF2 in myeloid cells lowered bacterial burdens. Their studies have brought to the fore the importance of NRF2 in regulating early interactions between M.tb. and host immune cells.

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