AI Article Synopsis
- Macrophages play a crucial role in fighting Mycobacterium tuberculosis (Mtb), but the bacteria can survive and replicate inside them, ultimately causing macrophage death and spreading the infection.
- Research using CRISPR-Cas9 screening revealed that type I interferons (IFNs) produced by macrophages are essential for the death of Mtb-infected macrophages in the lab.
- Blocking type I IFN signaling not only increased the effectiveness of rifampin, a common TB drug, but also suggests potential for developing more targeted therapies for tuberculosis.
Article Abstract
Macrophages help defend the host against Mycobacterium tuberculosis (Mtb), the major cause of tuberculosis (TB). Once phagocytized, Mtb resists killing by macrophages, replicates inside them, and leads to their death, releasing Mtb that can infect other cells. We found that the death of Mtb-infected mouse macrophages in vitro does not appear to proceed by a currently known pathway. Through genome-wide CRISPR-Cas9 screening, we identified a critical role for autocrine or paracrine signaling by macrophage-derived type I IFNs in the death of Mtb-infected macrophages in vitro, and blockade of type I IFN signaling augmented the effect of rifampin, a first-line TB drug, in Mtb-infected mice. Further definition of the pathway of type I IFN-mediated macrophage death may allow for host-directed therapy of TB that is more selective than systemic blockade of type I IFN signaling.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608065 | PMC |
| http://dx.doi.org/10.1084/jem.20200887 | DOI Listing |
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