| First Author | Chowdhury D | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 755961 | PubMed ID | 34867993 |
| Mgi Jnum | J:316444 | Mgi Id | MGI:6833184 |
| Doi | 10.3389/fimmu.2021.755961 | Citation | Chowdhury D, et al. (2021) Metallothionein 3-Zinc Axis Suppresses Caspase-11 Inflammasome Activation and Impairs Antibacterial Immunity. Front Immunol 12:755961 |
| abstractText | Non-canonical inflammasome activation by mouse caspase-11 (or human CASPASE-4/5) is crucial for the clearance of certain gram-negative bacterial infections, but can lead to severe inflammatory damage. Factors that promote non-canonical inflammasome activation are well recognized, but less is known about the mechanisms underlying its negative regulation. Herein, we identify that the caspase-11 inflammasome in mouse and human macrophages (Mvarphi) is negatively controlled by the zinc (Zn(2+)) regulating protein, metallothionein 3 (MT3). Upon challenge with intracellular lipopolysaccharide (iLPS), Mvarphi increased MT3 expression that curtailed the activation of caspase-11 and its downstream targets caspase-1 and interleukin (IL)-1beta. Mechanistically, MT3 increased intramacrophage Zn(2+) to downmodulate the TRIF-IRF3-STAT1 axis that is prerequisite for caspase-11 effector function. In vivo, MT3 suppressed activation of the caspase-11 inflammasome, while caspase-11 and MT3 synergized in impairing antibacterial immunity. The present study identifies an important yin-yang relationship between the non-canonical inflammasome and MT3 in controlling inflammation and immunity to gram-negative bacteria. |
