2024
J Exp Med. 2024 Jul 1;221(7):e20231814. doi: 10.1084/jem.20231814. Epub 2024 Apr 25.
Dual fluorescence reporter mice for Ccl3 transcription, translation, and intercellular communication
Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University Hospital of Bonn University , Bonn, Germany. Institute of Virology, Faculty of Medicine, University Hospital of Bonn University , Bonn, Germany. Institute for Virology, University Medical Center Mainz , Mainz, Germany.
Service type: Knock-in mice
Abstract
Chemokines guide immune cells during their response against pathogens and tumors. Various techniques exist to determine chemokine production, but none to identify cells that directly sense chemokines in vivo. We have generated CCL3-EASER (ErAse, SEnd, Receive) mice that simultaneously report for Ccl3 transcription and translation, allow identifying Ccl3-sensing cells, and permit inducible deletion of Ccl3-producing cells. We infected these mice with murine cytomegalovirus (mCMV), where Ccl3 and NK cells are critical defense mediators. We found that NK cells transcribed Ccl3 already in homeostasis, but Ccl3 translation required type I interferon signaling in infected organs during early infection. NK cells were both the principal Ccl3 producers and sensors of Ccl3, indicating auto/paracrine communication that amplified NK cell response, and this was essential for the early defense against mCMV. CCL3-EASER mice represent the prototype of a new class of dual fluorescence reporter mice for analyzing cellular communication via chemokines, which may be applied also to other chemokines and disease models.
Read Research Feature: Decoding NK cell signals: Insights into Chemokine-mediated immune responses >
