title: Induction of phagocytosis and intracellular signaling by an inhibitory channel catfish leukocyte immune-type receptor: evidence for immunoregulatory receptor functional plasticity in teleosts.
abstract: Immunoregulatory receptors are categorized as stimulatory or inhibitory based on their engagement of unique intracellular signaling networks. These proteins also display functional plasticity, which adds versatility to the control of innate immunity. Here we demonstrate that an inhibitory catfish leukocyte immune-type receptor (IpLITR) also displays stimulatory capabilities in a representative myeloid cell model. Previously, the receptor IpLITR 1.1b was shown to inhibit natural killer cell-mediated cytotoxicity. Here we expressed IpLITR 1.1b in rat basophilic leukemia-2H3 cells and monitored intracellular signaling and functional responses. Although IpLITR 1.1b did not stimulate cytokine secretion, activation of this receptor unexpectedly induced phagocytosis as well as extracellular signal-related kinase 1/2- and protein kinase B (Akt)-dependent signal transduction. This novel IpLITR 1.1b-mediated response was independent of an association with the FcRγ chain and was likely due to phosphotyrosine-dependent adaptors associating with prototypical signaling motifs within the distal region of its cytoplasmic tail. Furthermore, compared to a stimulatory IpLITR, IpLITR 1.1b displayed temporal differences in the induction of intracellular signaling, and IpLITR 1.1b-mediated phagocytosis had reduced sensitivity to EDTA and cytochalasin D. Overall, this is the first demonstration of functional plasticity for teleost LITRs, a process likely important for the fine-tuning of conserved innate defenses.
authors: Department of Biological Sciences, University of Alberta, Edmonton, Alta., Canada.
authors: Herman D
authors: HD
authors: Cortes
authors: Dustin M E
authors: DM
authors: Lillico
authors: Myron A
authors: MA
authors: Zwozdesky
authors: Joshua G
authors: JG
authors: Pemberton
authors: Allen
authors: A
authors: O'Brien
authors: Benjamin C S
authors: BC
authors: Montgomery
authors: Loes
authors: L
authors: Wiersma
authors: John P
authors: JP
authors: Chang
authors: James L
authors: JL
authors: Stafford
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007059:Ictaluridae; D007113:Immunity, Innate; D056747:Immunomodulation / Q000187:drug effects / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C111656:LIT receptor; D011971:Receptors, Immunologic; D015638:Cytochalasin D; D004492:Edetic Acid; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases