title: CRIg signals induce anti-intracellular bacterial phagosome activity in a chloride intracellular channel 3-dependent manner.
abstract: Macrophages provide a first line of defense against bacterial infection by engulfing and killing invading bacteria, but intracellular bacteria such as Listeria monocytogenes (LM) can survive in macrophages by various mechanisms of evasion. Complement receptor of the immunoglobulin (CRIg), a C3b receptor, binds to C3b on opsonized bacteria and facilitates clearance of the bacteria by promoting their uptake. We found that CRIg signaling induced by agonistic anti-CRIg mAb enhanced the killing of intracellular LM by macrophages, and that this occurred in LM-containing phagosomes. Chloride intra-cellular channel 3 CLIC3, an intracellular chloride channel protein, was essential for CRIg-mediated LM killing by directly interacting with the cytoplasmic domain of CRIg, and the two proteins colocalized on the membranes of LM-containing vacuoles. CLIC3(-/-) mice were as susceptible to LM as CRIg(-/-) mice. These findings identify a mechanism embedded in the process by which macrophages take up opsonized bacteria that prevents the bacteria from evading cell-mediated killing.
authors.affiliation: Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Korea.
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Kim
authors.forename: Beom K
authors.initials: BK
authors.lastname: Choi
authors.forename: Keoung M
authors.initials: KM
authors.lastname: Song
authors.forename: Ki W
authors.initials: KW
authors.lastname: Cha
authors.forename: Young H
authors.initials: YH
authors.lastname: Kim
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: In-Seob
authors.initials: IS
authors.lastname: Han
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005260:Female; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008561:Membrane Fusion / Q000276:immunology; D051379:Mice; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D010588:Phagosomes / Q000276:immunology*; D011485:Protein Binding; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014617:Vacuoles / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C509992:VSIG4 protein, mouse