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MACROPHAGES

ABCs of sepsis control

Nature Reviews Immunology volume 19, pages 200–201 (2019)Cite this article

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Millions of people die each year from sepsis — an immune-driven complication of infection. Death from bacterial sepsis can occur when there is a failure to switch from an initial hyperinflammatory phase to an endotoxin tolerance phase. The mechanisms underlying the switch between these phases have been unclear. A new study proposes that an ATP-binding cassette (ABC) family protein, ABCF1, has E2 ubiquitin-conjugating activity and regulates this shift by modulating TLR4 signalling and macrophage polarization.

Previous studies had linked ABCF1 to innate immune signalling and some autoimmune disorders, but its physiological function is unknown. Arora et al. show that knockdown of Abcf1 expression in bone marrow-derived macrophages (BMDMs) using small interfering RNA (siRNA) promoted M1 polarization and inhibited M2 polarization following LPS stimulation. Abcf1 siRNA-treated BMDMs also showed an increase in MyD88-dependent signalling (NF-κB activation) and a decrease in TRIF-dependent signalling (IRF3 activation), compared with control BMDMs. Accordingly, cytokine profiles were affected by the loss of ABCF1, resulting in increased M1-associated pro-inflammatory cytokines and decreased M2-associated anti-inflammatory cytokines.

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References

Original article

  • Arora, H. et al. The ATP-binding cassette gene ABCF1 functions as an E2 ubiquitin-conjugating enzyme controlling macrophage polarization to dampen lethal septic shock. Immunity 50, 418–431 (2019)

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Lucy Bird

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  1. Lucy Bird
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Correspondence to Lucy Bird.

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Bird, L. ABCs of sepsis control. Nat Rev Immunol 19, 200–201 (2019). https://doi.org/10.1038/s41577-019-0146-3

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  • DOI: https://doi.org/10.1038/s41577-019-0146-3

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