Research ArticleImmunology

A calcium-redox feedback loop controls human monocyte immune responses: The role of ORAI Ca2+ channels

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Science Signaling  08 Mar 2016:
Vol. 9, Issue 418, pp. ra26
DOI: 10.1126/scisignal.aaf1639

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Keeping monocytes in business

When monocytes of the immune system encounter a bacterial pathogen, they activate a calcium signaling pathway called SOCE, which is mediated by the ORAI/STIM complex. ORAI subunits form the Ca2+ channel; STIM is its activating partner. This calcium signal activates a plasma membrane enzyme that produces toxic reactive oxygen species (ROS) to kill the bacteria. Given that ROS also inactivate ORAI channels, how do the monocytes maintain signaling? Saul et al. found that human monocytes respond by altering the composition of the ORAI channel. ROS inhibit ORAI channels composed of ORAI1 subunits; however, if just one of the six channel subunits is ORAI3, then the channel resists this ROS-mediated inactivation. Human monocytes exposed to bacterial peptides in culture and phagocytes isolated from mice infected with bacteria increased the amount of ORAI3 and reduced the amount of ORAI1. This change in the ORAI3/ORAI1 ratio meant that more ROS-insensitive channels were present and the cells could continue to produce the appropriate calcium signal and mediate bacterial killing.

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